Is ARRDC3 p.Arg43Ser (c.129A>T) pathogenic?

ARRDC3 p.Arg43Ser (c.129A>T) is classified Uncertain significance in ARRDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely pathogenic (0.7406); Very rare (popmax 0.00127%, nfe).

How common is ARRDC3 p.Arg43Ser (c.129A>T) in the general population?

ARRDC3 p.Arg43Ser (c.129A>T) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about ARRDC3 p.Arg43Ser (c.129A>T)?

AlphaMissense predicts likely pathogenic (score 0.7406) — an in-silico prediction, not a clinical call.

ARRDC3 p.Arg43Ser

c.129A>T · VCV4643164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7406 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7406	likely pathogenic
REVEL	0.293	indeterminate
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 12 kb · p 4.7e-08 · regional, not allelic
Overall
CADD	28.6	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 0.00127% European (non-Finnish) · 15/1,180,038 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000929% 15/1,614,052 alleles · very rare

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: ARRDC3
Protein: p.Arg43Ser
Coding: c.129A>T
MANE Select: NM_020801
Type: single nucleotide variant
Location: chr5:91382964 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.36 · 3 PDB
Residue 43: a β-strand

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.Arg93Ile 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-arg43ser (accessed [today's date]).

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