Is HUWE1 p.Ala3826Val (c.11477C>T) pathogenic?

HUWE1 p.Ala3826Val (c.11477C>T) is classified Uncertain significance in HUWE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-22). AlphaMissense: likely benign (0.0854); Absent from gnomAD v4.1.

How common is HUWE1 p.Ala3826Val (c.11477C>T) in the general population?

HUWE1 p.Ala3826Val (c.11477C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HUWE1 p.Ala3826Val (c.11477C>T)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

HUWE1 p.Ala3826Val

c.11477C>T · VCV3764104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.082, phastCons 1
Regional constraint	o/e 1.28	unconstrained · MANE · 2,715 bp · p 0.2 · regional, not allelic
Overall
CADD	9.285	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 is an independent agreement signal.

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: HUWE1
Protein: p.Ala3826Val
Coding: c.11477C>T
MANE Select: NM_031407
Type: single nucleotide variant
Location: chrX:53539812 (GRCh38)
Residue 3826: the 'disordered' region

Full HUWE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HUWE1 c.567+1G>C Pathogenic ★★ same type
HUWE1 p.Arg110Gln Pathogenic ★★ same type
HUWE1 p.Arg2981His Pathogenic/Likely pathogenic ★★ same type
HUWE1 p.Arg3070Cys Pathogenic/Likely pathogenic ★★ same type
HUWE1 p.Arg3070His Pathogenic ★★ same type
HUWE1 p.Arg4013Trp Pathogenic/Likely pathogenic ★★ same type
HUWE1 p.Gly4217Ala Likely pathogenic ★★ same type
HUWE1 p.Gly4310Arg Pathogenic/Likely pathogenic ★★ 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/huwe1-p-ala3826val (accessed [today's date]).

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