Is CORO2A p.Val287Met (c.859G>A) pathogenic?

CORO2A p.Val287Met (c.859G>A) is classified Uncertain significance in CORO2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.1213); Ultra-rare (popmax 0.0294%, afr).

How common is CORO2A p.Val287Met (c.859G>A) in the general population?

CORO2A p.Val287Met (c.859G>A) is ultra-rare (popmax 0.0294%, afr) (gnomAD).

What do computational predictors say about CORO2A p.Val287Met (c.859G>A)?

AlphaMissense predicts likely benign (score 0.1213) — an in-silico prediction, not a clinical call.

CORO2A p.Val287Met

c.859G>A · VCV3835662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1213 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1213	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -4.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	donor gain · deltas
Pangolin	Δ0.38	gain · loss 0.12 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.12	GERP -3.7, phastCons 0.69
Regional constraint	o/e 0.89	unconstrained · MANE · 33 kb · p 0.0046 · regional, not allelic
Overall
CADD	19.96	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0294% African / African-American · 22/74,904 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00248% 40/1,613,606 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0294%	3,405
East Asian	0.00669%	14,957
South Asian	0.0044%	22,748
Admixed American	0.00334%	29,982
Remaining individualsnot grpmax-eligible	0.0032%	31,228
European (non-Finnish)	0.000593%	168,550

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: CORO2A
Protein: p.Val287Met
Coding: c.859G>A
MANE Select: NM_052820
Type: single nucleotide variant
Location: chr9:98130966 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.12

Full CORO2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CORO2A p.Ala105Asp Uncertain significance ★ ⚠ same type
CORO2A p.Ala132Thr Uncertain significance ★ ⚠ same type
CORO2A p.Ala144Thr Uncertain significance ★ ⚠ same type
CORO2A p.Ala145Thr Uncertain significance ★ ⚠ same type
CORO2A p.Ala218Thr Uncertain significance ★ ⚠ same type
CORO2A p.Ala280Thr Uncertain significance ★ ⚠ same type
CORO2A p.Ala59Ser Uncertain significance ★ ⚠ same type
CORO2A p.Ala59Thr Uncertain significance ★ ⚠ same type

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/coro2a-p-val287met (accessed [today's date]).

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