Is CORO2A p.Arg248Trp (c.742C>T) pathogenic?

CORO2A p.Arg248Trp (c.742C>T) is classified Uncertain significance in CORO2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely pathogenic (0.9264); Ultra-rare (popmax 0.0117%, amr).

How common is CORO2A p.Arg248Trp (c.742C>T) in the general population?

CORO2A p.Arg248Trp (c.742C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about CORO2A p.Arg248Trp (c.742C>T)?

AlphaMissense predicts likely pathogenic (score 0.9264) — an in-silico prediction, not a clinical call.

CORO2A p.Arg248Trp

c.742C>T · rs377675370 · VCV3076393

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9264 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9264	likely pathogenic
REVEL	0.35	indeterminate
SaProt	LLR -10.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP -1.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 33 kb · p 0.0046 · regional, not allelic
Overall
CADD	29.6	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 0.0117% Admixed American · 7/60,030 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00297% 48/1,614,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,576
African / African-American	0.00666%	15,011
South Asian	0.00549%	18,217
Remaining individualsnot grpmax-eligible	0.0032%	31,253
European (non-Finnish)	0.00246%	40,689

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.Arg248Trp
Coding: c.742C>T
MANE Select: NM_052820
dbSNP: rs377675370
Type: single nucleotide variant
Location: chr9:98132208 (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-arg248trp (accessed [today's date]).

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