Is CORO2B p.Val67Ile (c.199G>A) pathogenic?

CORO2B p.Val67Ile (c.199G>A) is classified Uncertain significance in CORO2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely benign (0.0967); Ultra-rare (popmax 0.0401%, amr).

How common is CORO2B p.Val67Ile (c.199G>A) in the general population?

CORO2B p.Val67Ile (c.199G>A) is ultra-rare (popmax 0.0401%, amr) (gnomAD).

What do computational predictors say about CORO2B p.Val67Ile (c.199G>A)?

AlphaMissense predicts likely benign (score 0.0967) — an in-silico prediction, not a clinical call.

CORO2B p.Val67Ile

c.199G>A · rs749693049 · VCV3076403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0967 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0967	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -10.62	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 9.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 140 kb · p 2.5e-16 · regional, not allelic
Overall
CADD	28.3	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 0.0401% Admixed American · 24/59,918 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0235%

Overall 0.00478% 77/1,611,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0401%	2,497
East Asian	0.0335%	2,987
Remaining individualsnot grpmax-eligible	0.008%	12,495
European (non-Finnish)	0.0028%	35,755

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: CORO2B
Protein: p.Val67Ile
Coding: c.199G>A
MANE Select: NM_006091
dbSNP: rs749693049
Type: single nucleotide variant
Location: chr15:68645343 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 91.58

Full CORO2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CORO2B p.Ala334Val Uncertain significance ★ ⚠ same type
CORO2B p.Ala60Thr Uncertain significance ★ ⚠ same type
CORO2B p.Arg124Gln Uncertain significance ★ ⚠ same type
CORO2B p.Arg13His Uncertain significance ★ ⚠ same type
CORO2B p.Arg213His Uncertain significance ★ ⚠ same type
CORO2B p.Arg227Gln Uncertain significance ★ ⚠ same type
CORO2B p.Arg236Gln Uncertain significance ★ ⚠ same type
CORO2B p.Arg244Thr 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/coro2b-p-val67ile (accessed [today's date]).

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