Is AMER1 p.Cys822Phe (c.2465G>T) pathogenic?

AMER1 p.Cys822Phe (c.2465G>T) is classified Uncertain significance in AMER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-24). AlphaMissense: ambiguous (0.3563); Absent from gnomAD v4.1.

How common is AMER1 p.Cys822Phe (c.2465G>T) in the general population?

AMER1 p.Cys822Phe (c.2465G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMER1 p.Cys822Phe (c.2465G>T)?

AlphaMissense predicts ambiguous (score 0.3563) — an in-silico prediction, not a clinical call.

AMER1 p.Cys822Phe

c.2465G>T · rs371470486 · VCV2125292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3563 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3563	ambiguous
REVEL	0.259	benign-leaning
SaProt	LLR -5.65	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,404 bp · p 0.037 · regional, not allelic
Overall
CADD	24.8	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: AMER1
Protein: p.Cys822Phe
Coding: c.2465G>T
MANE Select: NM_152424
dbSNP: rs371470486
Type: single nucleotide variant
Location: chrX:64190822 (GRCh38)
Structure: AlphaFold pLDDT 48.88 · 3 PDB

Full AMER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMER1 p.Arg353Ter Pathogenic ★★ same type
AMER1 p.Arg358Ter Pathogenic ★★ same type
AMER1 p.Arg497Ter Pathogenic/Likely pathogenic ★★ same type
AMER1 p.Gln189Ter Pathogenic ★★ same type
AMER1 p.Gln335Ter Pathogenic ★★ same type
AMER1 p.Glu191Ter Pathogenic/Likely pathogenic ★★ same type
AMER1 p.Ala202Gly Uncertain significance ★★ ⚠ same type
AMER1 p.Ala229Pro 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/amer1-p-cys822phe (accessed [today's date]).

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