Is CORO1A p.Ser299= (c.897C>T) pathogenic?

CORO1A p.Ser299= (c.897C>T) is classified Benign/Likely benign in CORO1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-13). Ultra-rare (popmax 0.0593%, sas); Associated with severe combined immunodeficiency due to CORO1A deficiency.

What condition is associated with CORO1A p.Ser299= (c.897C>T)?

CORO1A p.Ser299= (c.897C>T) is associated with severe combined immunodeficiency due to CORO1A deficiency (ClinVar).

How common is CORO1A p.Ser299= (c.897C>T) in the general population?

CORO1A p.Ser299= (c.897C>T) is ultra-rare (popmax 0.0593%, sas) (gnomAD).

CORO1A p.Ser299=

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.897C>T · rs535362943 · VCV1169122

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0593%, sas)

Conditions

severe combined immunodeficiency due to CORO1A deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -15
Overall
CADD	6.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0593% South Asian · 54/91,082 alleles

Filtering AF 0.0466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0421%

Overall 0.00465% 75/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0593%	1,687
Admixed American	0.005%	20,006
Remaining individualsnot grpmax-eligible	0.0032%	31,254
African / African-American	0.00133%	75,018
European (non-Finnish)	0.00127%	78,668

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.Ser299=
Coding: c.897C>T
MANE Select: NM_007074
dbSNP: rs535362943
Type: single nucleotide variant
Location: chr16:30187977 (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-ser299 (accessed [today's date]).

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