Is ARIH1 p.Glu26Val (c.77A>T) pathogenic?

ARIH1 p.Glu26Val (c.77A>T) is classified Uncertain significance in ARIH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-11). AlphaMissense: likely benign (0.1256); Absent from gnomAD v4.1.

How common is ARIH1 p.Glu26Val (c.77A>T) in the general population?

ARIH1 p.Glu26Val (c.77A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARIH1 p.Glu26Val (c.77A>T)?

AlphaMissense predicts likely benign (score 0.1256) — an in-silico prediction, not a clinical call.

ARIH1 p.Glu26Val

c.77A>T · rs2140386460 · VCV2289164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1256 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1256	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -8.96	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 10	GERP 1.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 365 bp · p 0.039 · regional, not allelic
Overall
CADD	24.1	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: ARIH1
Protein: p.Glu26Val
Coding: c.77A>T
MANE Select: NM_005744
dbSNP: rs2140386460
Type: single nucleotide variant
Location: chr15:72474716 (GRCh38)
Gene constraint: LOEUF 0.302 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.71 · 10 PDB
Residue 26: the 'disordered' region

Full ARIH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARIH1 p.Glu26Ala Uncertain significance ★ ⚠ same residue
ARIH1 p.Glu26Gly Uncertain significance ★ ⚠ same residue
ARIH1 p.Arg173Cys Uncertain significance ★★ same type
ARIH1 p.Arg296Cys Uncertain significance ★★ ⚠ same type
ARIH1 p.Asn139Ser Uncertain significance ★★ ⚠ same type
ARIH1 p.Glu49Asp Uncertain significance ★★ ⚠ same type
ARIH1 p.Glu57Gln Uncertain significance ★★ ⚠ same type
ARIH1 p.Gly64Arg 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/arih1-p-glu26val (accessed [today's date]).

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