Is CORO2A p.Val29Met (c.85G>A) pathogenic?

CORO2A p.Val29Met (c.85G>A) is classified Uncertain significance in CORO2A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: ambiguous (0.4162); Ultra-rare (popmax 0.0164%, mid).

How common is CORO2A p.Val29Met (c.85G>A) in the general population?

CORO2A p.Val29Met (c.85G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CORO2A p.Val29Met (c.85G>A)?

AlphaMissense predicts ambiguous (score 0.4162) — an in-silico prediction, not a clinical call.

CORO2A p.Val29Met

c.85G>A · rs201807340 · VCV2341462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4162 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
AlphaMissense	0.4162	ambiguous
REVEL	0.449	indeterminate
SaProt	LLR -10.32	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.82, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 33 kb · p 0.0046 · regional, not allelic
Overall
CADD	28.9	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0127%

Overall 0.0132% 213/1,614,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,691
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.0153%	6,556
Remaining individualsnot grpmax-eligible	0.0144%	6,942
Admixed American	0.00833%	11,999
East Asian	0.00445%	22,448
African / African-American	0.004%	24,973
Finnishnot grpmax-eligible	0.00156%	64,034
South Asian	0.0011%	91,086

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val29Met
Coding: c.85G>A
MANE Select: NM_052820
dbSNP: rs201807340
Type: single nucleotide variant
Location: chr9:98157576 (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-val29met (accessed [today's date]).

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