Is CORO1A p.Pro223= (c.669C>T) pathogenic?

CORO1A p.Pro223= (c.669C>T) is classified Likely benign in CORO1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-06). Very rare (popmax 0.00768%, sas); Associated with severe combined immunodeficiency due to CORO1A deficiency.

What condition is associated with CORO1A p.Pro223= (c.669C>T)?

CORO1A p.Pro223= (c.669C>T) is associated with severe combined immunodeficiency due to CORO1A deficiency (ClinVar).

How common is CORO1A p.Pro223= (c.669C>T) in the general population?

CORO1A p.Pro223= (c.669C>T) is very rare (popmax 0.00768%, sas) (gnomAD).

CORO1A p.Pro223=

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.669C>T · VCV4743691

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

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 -14
Overall
CADD	0.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00768% South Asian · 7/91,092 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000869% 14/1,611,184 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00768%	13,013
African / African-American	0.00133%	74,938
European (non-Finnish)	0.000508%	196,668

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.Pro223=
Coding: c.669C>T
MANE Select: NM_007074
Type: single nucleotide variant
Location: chr16:30187414 (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-pro223 (accessed [today's date]).

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