Is CORO1A p.Pro75Ser (c.223C>T) pathogenic?

CORO1A p.Pro75Ser (c.223C>T) is classified Uncertain significance in CORO1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: likely benign (0.2978); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with CORO1A p.Pro75Ser (c.223C>T)?

CORO1A p.Pro75Ser (c.223C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CORO1A p.Pro75Ser (c.223C>T) in the general population?

CORO1A p.Pro75Ser (c.223C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CORO1A p.Pro75Ser (c.223C>T)?

AlphaMissense predicts likely benign (score 0.2978) — an in-silico prediction, not a clinical call.

CORO1A p.Pro75Ser

c.223C>T · VCV3269009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2978 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2978	likely benign
REVEL	0.43	indeterminate
SaProt	LLR -11.33	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 3,196 bp · p 7.1e-18 · regional, not allelic
Overall
CADD	24.9	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 0.00134% African / African-American · 1/74,862 alleles

Overall 0.000657% 1/152,200 alleles · very rare

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.Pro75Ser
Coding: c.223C>T
MANE Select: NM_007074
Type: single nucleotide variant
Location: chr16:30186622 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CORO1A p.Pro75= Likely benign ★ same residue
CORO1A p.Arg186Gln Uncertain significance ★★ ⚠ same condition
CORO1A p.Arg293Trp Uncertain significance ★★ ⚠ same condition
CORO1A p.Arg414His Uncertain significance ★★ ⚠ same condition
CORO1A p.Gly413Arg Uncertain significance ★★ ⚠ same condition
CORO1A p.Pro119Arg Uncertain significance ★★ ⚠ same condition
CORO1A p.Pro217Thr Uncertain significance ★★ ⚠ same condition
CORO1A p.Ser427Leu 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-pro75ser (accessed [today's date]).

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