Is ARRDC5 p.Ala90Ser (c.268G>T) pathogenic?

ARRDC5 p.Ala90Ser (c.268G>T) is classified Uncertain significance in ARRDC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.1325); Rare (popmax 0.112%, afr).

How common is ARRDC5 p.Ala90Ser (c.268G>T) in the general population?

ARRDC5 p.Ala90Ser (c.268G>T) is rare (popmax 0.112%, afr) (gnomAD).

What do computational predictors say about ARRDC5 p.Ala90Ser (c.268G>T)?

AlphaMissense predicts likely benign (score 0.1325) — an in-silico prediction, not a clinical call.

ARRDC5 p.Ala90Ser

c.268G>T · rs199894807 · VCV2385712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1325 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1325	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -5.96	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 7.1	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 12 kb · p 0.54 · regional, not allelic
Overall
CADD	19.93	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 A104S vs ClinVar A90S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.112% African / African-American · 84/74,914 alleles

Filtering AF 0.0927% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0856%

Overall 0.00564% 91/1,613,216 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.112%	892
Remaining individualsnot grpmax-eligible	0.0048%	20,822
Admixed American	0.00334%	29,978
European (non-Finnish)	0.00017%	589,776

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ARRDC5
Protein: p.Ala90Ser
Coding: c.268G>T
MANE Select: NM_001080523
dbSNP: rs199894807
Type: single nucleotide variant
Location: chr19:4896862 (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

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.Arg135Gly Uncertain significance ★ ⚠ same type
ARRDC5 p.Arg227Trp Uncertain significance ★ ⚠ same type
ARRDC5 p.Arg247His 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-ala90ser (accessed [today's date]).

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