Is ARRDC1 p.Arg3Leu (c.8G>T) pathogenic?

ARRDC1 p.Arg3Leu (c.8G>T) is classified Uncertain significance in ARRDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: ambiguous (0.4607); Very rare (popmax 0.00244%, nfe).

How common is ARRDC1 p.Arg3Leu (c.8G>T) in the general population?

ARRDC1 p.Arg3Leu (c.8G>T) is very rare (popmax 0.00244%, nfe) (gnomAD).

What do computational predictors say about ARRDC1 p.Arg3Leu (c.8G>T)?

AlphaMissense predicts ambiguous (score 0.4607) — an in-silico prediction, not a clinical call.

ARRDC1 p.Arg3Leu

c.8G>T · rs750001196 · VCV2559950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4607	ambiguous
REVEL	0.055	moderately benign-leaning
SaProt	LLR -8.95	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.82, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 9,417 bp · p 0.014 · regional, not allelic
Overall
CADD	25.4	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 0.00244% European (non-Finnish) · 26/1,064,804 alleles

Filtering AF 0.0017% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00144%

Overall 0.00195% 27/1,382,614 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00244%	40,954
African / African-American	0.00151%	66,040

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.Arg3Leu
Coding: c.8G>T
MANE Select: NM_152285
dbSNP: rs750001196
Type: single nucleotide variant
Location: chr9:137605725 (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-arg3leu (accessed [today's date]).

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