Is REV1 p.Pro765Ala (c.2293C>G) pathogenic?

REV1 p.Pro765Ala (c.2293C>G) is classified Uncertain significance in REV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: ambiguous (0.5157); Absent from gnomAD v4.1.

How common is REV1 p.Pro765Ala (c.2293C>G) in the general population?

REV1 p.Pro765Ala (c.2293C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about REV1 p.Pro765Ala (c.2293C>G)?

AlphaMissense predicts ambiguous (score 0.5157) — an in-silico prediction, not a clinical call.

REV1 p.Pro765Ala

c.2293C>G · rs2545091331 · VCV2618031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5157 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5157	ambiguous
REVEL	0.341	indeterminate
SaProt	LLR -5.31	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 24 kb · p 5.1e-07 · regional, not allelic
Overall
CADD	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: REV1
Protein: p.Pro765Ala
Coding: c.2293C>G
MANE Select: NM_016316
dbSNP: rs2545091331
Type: single nucleotide variant
Location: chr2:99410747 (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.Pro765Ser Uncertain significance ★ ⚠ same residue
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

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-pro765ala (accessed [today's date]).

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