Is CORO1A p.Arg293Trp (c.877C>T) pathogenic?

CORO1A p.Arg293Trp (c.877C>T) is classified Uncertain significance in CORO1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-09). AlphaMissense: likely pathogenic (0.9408); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CORO1A p.Arg293Trp (c.877C>T)?

CORO1A p.Arg293Trp (c.877C>T) is associated with Inborn genetic diseases, severe combined immunodeficiency due to CORO1A deficiency (ClinVar).

How common is CORO1A p.Arg293Trp (c.877C>T) in the general population?

CORO1A p.Arg293Trp (c.877C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CORO1A p.Arg293Trp (c.877C>T)?

AlphaMissense predicts likely pathogenic (score 0.9408) — an in-silico prediction, not a clinical call.

CORO1A p.Arg293Trp

c.877C>T · rs1262973323 · VCV1063698

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9408 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9408	likely pathogenic
REVEL	0.619	indeterminate
SaProt	LLR -15.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 3,196 bp · p 7.1e-18 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,002 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,934 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.Arg293Trp
Coding: c.877C>T
MANE Select: NM_007074
dbSNP: rs1262973323
Type: single nucleotide variant
Location: chr16:30187957 (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

Also linked: severe combined immunodeficiency due to CORO1A deficiency

Similar variants

CORO1A p.Arg293Gln Uncertain significance ★★ ⚠ same residue
CORO1A p.Ala385Val Uncertain significance ★★ ⚠ same condition
CORO1A p.Arg186Gln Uncertain significance ★★ ⚠ same condition
CORO1A p.Arg414His 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-arg293trp (accessed [today's date]).

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