Is AMER3 p.Val238Ala (c.713T>C) pathogenic?

AMER3 p.Val238Ala (c.713T>C) is classified Uncertain significance in AMER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.2965); Absent from gnomAD v4.1.

How common is AMER3 p.Val238Ala (c.713T>C) in the general population?

AMER3 p.Val238Ala (c.713T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMER3 p.Val238Ala (c.713T>C)?

AlphaMissense predicts likely benign (score 0.2965) — an in-silico prediction, not a clinical call.

AMER3 p.Val238Ala

c.713T>C · VCV4640202

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2965 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2965	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -5.74	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 5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 2,582 bp · p 0.068 · regional, not allelic
Overall
CADD	23.5	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

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: AMER3
Protein: p.Val238Ala
Coding: c.713T>C
MANE Select: NM_152698
Type: single nucleotide variant
Location: chr2:130762785 (GRCh38)
Structure: AlphaFold pLDDT 45.30

Full AMER3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMER3 p.Val238Met Uncertain significance ★ ⚠ same residue
AMER3 p.Ala175Val Uncertain significance ★ ⚠ same type
AMER3 p.Ala25Thr Uncertain significance ★ ⚠ same type
AMER3 p.Ala345Ser Uncertain significance ★ ⚠ same type
AMER3 p.Ala402Asp Uncertain significance ★ ⚠ same type
AMER3 p.Ala557Thr Uncertain significance ★ ⚠ same type
AMER3 p.Ala55Thr Uncertain significance ★ ⚠ same type
AMER3 p.Ala579Thr 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/amer3-p-val238ala (accessed [today's date]).

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