Is CORO1A p.Ser268= (c.804C>T) pathogenic?

CORO1A p.Ser268= (c.804C>T) is classified Benign/Likely benign in CORO1A (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-25). Low-frequency (popmax 1%, afr); Associated with severe combined immunodeficiency due to CORO1A deficiency.

What condition is associated with CORO1A p.Ser268= (c.804C>T)?

CORO1A p.Ser268= (c.804C>T) is associated with severe combined immunodeficiency due to CORO1A deficiency (ClinVar).

How common is CORO1A p.Ser268= (c.804C>T) in the general population?

CORO1A p.Ser268= (c.804C>T) is low-frequency (popmax 1%, afr) (gnomAD).

CORO1A p.Ser268=

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.804C>T · rs149867063 · VCV381252

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1%, afr)

Conditions

severe combined immunodeficiency due to CORO1A deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10
Overall
CADD	2.491	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1% African / African-American · 716/71,580 alleles

Filtering AF 0.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.915%

Overall 0.0984% 1,530/1,554,798 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1%	100
Middle Eastern	0.365%	274
Admixed American	0.318%	314
Remaining individualsnot grpmax-eligible	0.221%	452
European (non-Finnish)	0.0413%	2,420
South Asian	0.00554%	18,037
East Asian	0.00504%	19,850

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.Ser268=
Coding: c.804C>T
MANE Select: NM_007074
dbSNP: rs149867063
Type: single nucleotide variant
Location: chr16:30187772 (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-ser268 (accessed [today's date]).

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