Is ARRDC1 p.Thr348Ala (c.1042A>G) pathogenic?

ARRDC1 p.Thr348Ala (c.1042A>G) is classified Likely benign in ARRDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: likely benign (0.056); Rare (popmax 0.103%, afr).

How common is ARRDC1 p.Thr348Ala (c.1042A>G) in the general population?

ARRDC1 p.Thr348Ala (c.1042A>G) is rare (popmax 0.103%, afr) (gnomAD).

What do computational predictors say about ARRDC1 p.Thr348Ala (c.1042A>G)?

AlphaMissense predicts likely benign (score 0.056) — an in-silico prediction, not a clinical call.

ARRDC1 p.Thr348Ala

c.1042A>G · rs754382552 · VCV2302186

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.056 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.056	likely benign
REVEL	0.001	strongly benign-leaning
SaProt	LLR -5.50	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 -1.7	GERP -10
Regional constraint	o/e 1.10	unconstrained · MANE · 9,417 bp · p 0.014 · regional, not allelic
Overall
CADD	0.007	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% African / African-American · 77/74,658 alleles

Filtering AF 0.0845% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0777%

Overall 0.00496% 80/1,612,100 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.103%	970
Admixed American	0.00501%	19,965

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: ARRDC1
Protein: p.Thr348Ala
Coding: c.1042A>G
MANE Select: NM_152285
dbSNP: rs754382552
Type: single nucleotide variant
Location: chr9:137614805 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34

Full ARRDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARRDC1 p.Ala223Val Uncertain significance ★ ⚠ same type
ARRDC1 p.Ala228Val Uncertain significance ★ ⚠ same type
ARRDC1 p.Ala25Ser Uncertain significance ★ ⚠ same type
ARRDC1 p.Ala285Thr Uncertain significance ★ ⚠ same type
ARRDC1 p.Ala311Thr Uncertain significance ★ ⚠ same type
ARRDC1 p.Ala34Val Uncertain significance ★ ⚠ same type
ARRDC1 p.Ala94Val Uncertain significance ★ ⚠ same type
ARRDC1 p.Arg119Gln 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/arrdc1-p-thr348ala (accessed [today's date]).

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