Is REV1 p.Cys511Arg (c.1531T>C) pathogenic?

REV1 p.Cys511Arg (c.1531T>C) is classified Uncertain significance in REV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-18). AlphaMissense: likely pathogenic (0.9753); Very rare (popmax 0.00114%, sas).

How common is REV1 p.Cys511Arg (c.1531T>C) in the general population?

REV1 p.Cys511Arg (c.1531T>C) is very rare (popmax 0.00114%, sas) (gnomAD).

What do computational predictors say about REV1 p.Cys511Arg (c.1531T>C)?

AlphaMissense predicts likely pathogenic (score 0.9753) — an in-silico prediction, not a clinical call.

REV1 p.Cys511Arg

c.1531T>C · VCV3788384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00114%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9753	likely pathogenic · top 6% in REV1
REVEL	0.882	moderately pathogenic-leaning
SaProt	LLR -18.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 24 kb · p 5.1e-07 · regional, not allelic
Overall
CADD	29.3	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 0.00114% South Asian · 1/87,622 alleles

Overall 6.26e-05% 1/1,598,610 alleles · very rare exomes 1/1,446,784 · genomes 0/151,826 · joint denominator

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: REV1
Protein: p.Cys511Arg
Coding: c.1531T>C
MANE Select: NM_016316
Type: single nucleotide variant
Location: chr2:99429856 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.20 · 17 PDB
Residue 511: the umuc domain; a β-strand

Full REV1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

REV1 p.Leu1131His Benign ★★ same type
REV1 p.Ala335Thr Uncertain significance ★ ⚠ same type
REV1 p.Ala494Val Uncertain significance ★ ⚠ same type
REV1 p.Ala581Gly Uncertain significance ★ ⚠ same type
REV1 p.Ala789Thr Uncertain significance ★ ⚠ same type
REV1 p.Ala907Asp Uncertain significance ★ ⚠ same type
REV1 p.Arg219Ser Uncertain significance ★ ⚠ same type
REV1 p.Arg290Gln 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/rev1-p-cys511arg (accessed [today's date]).

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