Is CORO1A p.Ser8Phe (c.23C>T) pathogenic?

CORO1A p.Ser8Phe (c.23C>T) is classified Uncertain significance in CORO1A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-31). AlphaMissense: likely pathogenic (0.604); Very rare (popmax 0.00305%, nfe); Associated with severe combined immunodeficiency due to CORO1A deficiency.

What condition is associated with CORO1A p.Ser8Phe (c.23C>T)?

CORO1A p.Ser8Phe (c.23C>T) is associated with severe combined immunodeficiency due to CORO1A deficiency (ClinVar).

How common is CORO1A p.Ser8Phe (c.23C>T) in the general population?

CORO1A p.Ser8Phe (c.23C>T) is very rare (popmax 0.00305%, nfe) (gnomAD).

What do computational predictors say about CORO1A p.Ser8Phe (c.23C>T)?

AlphaMissense predicts likely pathogenic (score 0.604) — an in-silico prediction, not a clinical call.

CORO1A p.Ser8Phe

Q: How is Severe combined immunodeficiency due to CORO1A deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.23C>T · rs763479989 · VCV1014798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00305%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

severe combined immunodeficiency due to CORO1A deficiency

Computational evidence

Protein change
AlphaMissense	0.604	likely pathogenic
REVEL	0.223	benign-leaning
SaProt	LLR -10.84	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 3,196 bp · p 7.1e-18 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00305% European (non-Finnish) · 36/1,180,016 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00274% 40/1,461,814 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)grpmax	0.00305%	32,778
Finnishnot grpmax-eligible	0.00156%	63,994

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CORO1A
Protein: p.Ser8Phe
Coding: c.23C>T
MANE Select: NM_007074
dbSNP: rs763479989
Type: single nucleotide variant
Location: chr16:30185232 (GRCh38)
Gene constraint: LOEUF 0.572 · pLI 0.71 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.25

Full CORO1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe combined immunodeficiency due to CORO1A deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe combined immunodeficiency due to CORO1A deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

CORO1A p.Ala385Val Uncertain significance ★★ ⚠ same condition
CORO1A p.Arg186Gln Uncertain significance ★★ ⚠ same condition
CORO1A p.Arg293Gln Uncertain significance ★★ ⚠ same condition
CORO1A p.Arg293Trp Uncertain significance ★★ ⚠ same condition
CORO1A p.Gly413Arg Uncertain significance ★★ ⚠ same condition
CORO1A p.His92Gln Uncertain significance ★★ ⚠ same condition
CORO1A p.Leu116Pro Uncertain significance ★★ same condition
CORO1A p.Met167Thr Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/coro1a-p-ser8phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown