Is ARRDC5 p.Pro12Ala (c.34C>G) pathogenic?

ARRDC5 p.Pro12Ala (c.34C>G) is classified Uncertain significance in ARRDC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: likely benign (0.1619); Absent from gnomAD v4.1.

How common is ARRDC5 p.Pro12Ala (c.34C>G) in the general population?

ARRDC5 p.Pro12Ala (c.34C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARRDC5 p.Pro12Ala (c.34C>G)?

AlphaMissense predicts likely benign (score 0.1619) — an in-silico prediction, not a clinical call.

ARRDC5 p.Pro12Ala

c.34C>G · VCV3432167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1619 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1619	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -8.36	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 9.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 12 kb · p 0.54 · regional, not allelic
Overall
CADD	22.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P26A vs ClinVar P12A) — verify the residue.

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: ARRDC5
Protein: p.Pro12Ala
Coding: c.34C>G
MANE Select: NM_001080523
Type: single nucleotide variant
Location: chr19:4902792 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.19

Full ARRDC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UHRF1 p.Gln12His Uncertain significance ★ ⚠ same residue
ARRDC5 c.-15A>T Uncertain significance ★ ⚠ same type
ARRDC5 c.-24T>C Uncertain significance ★ ⚠ same type
ARRDC5 p.Ala241Val Uncertain significance ★ ⚠ same type
ARRDC5 p.Ala305Asp Uncertain significance ★ ⚠ same type
ARRDC5 p.Ala305Thr Uncertain significance ★ ⚠ same type
ARRDC5 p.Ala90Ser Uncertain significance ★ ⚠ same type
ARRDC5 p.Arg135Gly 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/arrdc5-p-pro12ala (accessed [today's date]).

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