Is ARRDC3 p.Tyr24His (c.70T>C) pathogenic?

ARRDC3 p.Tyr24His (c.70T>C) is classified Uncertain significance in ARRDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely pathogenic (0.8893); Absent from gnomAD v4.1.

How common is ARRDC3 p.Tyr24His (c.70T>C) in the general population?

ARRDC3 p.Tyr24His (c.70T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARRDC3 p.Tyr24His (c.70T>C)?

AlphaMissense predicts likely pathogenic (score 0.8893) — an in-silico prediction, not a clinical call.

ARRDC3 p.Tyr24His

c.70T>C · rs780018247 · VCV2238966

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8893 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8893	likely pathogenic
REVEL	0.436	indeterminate
SaProt	LLR -10.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 12 kb · p 4.7e-08 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ARRDC3
Protein: p.Tyr24His
Coding: c.70T>C
MANE Select: NM_020801
dbSNP: rs780018247
Type: single nucleotide variant
Location: chr5:91383023 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.36 · 3 PDB

Full ARRDC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARRDC3 p.Ala227Thr Uncertain significance ★ ⚠ same type
ARRDC3 p.Ala65Thr Uncertain significance ★ ⚠ same type
ARRDC3 p.Arg109Gly Uncertain significance ★ ⚠ same type
ARRDC3 p.Arg135His Uncertain significance ★ ⚠ same type
ARRDC3 p.Arg284His Uncertain significance ★ ⚠ same type
ARRDC3 p.Arg414Cys Uncertain significance ★ ⚠ same type
ARRDC3 p.Arg414His Uncertain significance ★ ⚠ same type
ARRDC3 p.Arg43Ser 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/arrdc3-p-tyr24his (accessed [today's date]).

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