Is CORO2B p.Thr180Met (c.539C>T) pathogenic?

CORO2B p.Thr180Met (c.539C>T) is classified Uncertain significance in CORO2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-23). AlphaMissense: likely benign (0.0837); Very rare (popmax 0.00297%, nfe).

How common is CORO2B p.Thr180Met (c.539C>T) in the general population?

CORO2B p.Thr180Met (c.539C>T) is very rare (popmax 0.00297%, nfe) (gnomAD).

What do computational predictors say about CORO2B p.Thr180Met (c.539C>T)?

AlphaMissense predicts likely benign (score 0.0837) — an in-silico prediction, not a clinical call.

CORO2B p.Thr180Met

c.539C>T · rs779907122 · VCV2329407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0837	likely benign
REVEL	0.315	indeterminate
SaProt	LLR -6.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.82, phastCons 0.99
Regional constraint	o/e 0.65	unconstrained · MANE · 140 kb · p 2.5e-16 · regional, not allelic
Overall
CADD	23.4	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 0.00297% European (non-Finnish) · 35/1,179,960 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00242% 39/1,614,038 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00297%	33,713
East Asian	0.00223%	44,880
Admixed American	0.00167%	59,982
African / African-American	0.00133%	75,052
South Asian	0.0011%	91,050

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.Thr180Met
Coding: c.539C>T
MANE Select: NM_006091
dbSNP: rs779907122
Type: single nucleotide variant
Location: chr15:68711597 (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.Thr180= Likely benign ★ same residue
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

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-thr180met (accessed [today's date]).

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