Is REV1 p.Ser882Pro (c.2644T>C) pathogenic?

REV1 p.Ser882Pro (c.2644T>C) is classified Likely benign in REV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.0603); Ultra-rare (popmax 0.0329%, mid).

How common is REV1 p.Ser882Pro (c.2644T>C) in the general population?

REV1 p.Ser882Pro (c.2644T>C) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about REV1 p.Ser882Pro (c.2644T>C)?

AlphaMissense predicts likely benign (score 0.0603) — an in-silico prediction, not a clinical call.

REV1 p.Ser882Pro

c.2644T>C · rs780806643 · VCV2365607

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0603 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0603	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -5.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.67	GERP -4.1
Regional constraint	o/e 0.77	unconstrained · MANE · 24 kb · p 5.1e-07 · regional, not allelic
Overall
CADD	0.016	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 0.0329% Middle Eastern · 2/6,080 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00738% 119/1,613,368 alleles · ultra-rare exomes 111/1,461,170 · genomes 8/152,198 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,040
East Asian	0.029%	3,452
Admixed American	0.0167%	5,985
European (non-Finnish)	0.00763%	13,110
Remaining individualsnot grpmax-eligible	0.0032%	31,229
African / African-American	0.00267%	37,433

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.Ser882Pro
Coding: c.2644T>C
MANE Select: NM_016316
dbSNP: rs780806643
Type: single nucleotide variant
Location: chr2:99406077 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.20 · 17 PDB

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-ser882pro (accessed [today's date]).

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