Is ARRDC3 p.His103Tyr (c.307C>T) pathogenic?

ARRDC3 p.His103Tyr (c.307C>T) is classified Uncertain significance in ARRDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: likely benign (0.0774); Very rare (popmax 0.00622%, nfe).

How common is ARRDC3 p.His103Tyr (c.307C>T) in the general population?

ARRDC3 p.His103Tyr (c.307C>T) is very rare (popmax 0.00622%, nfe) (gnomAD).

What do computational predictors say about ARRDC3 p.His103Tyr (c.307C>T)?

AlphaMissense predicts likely benign (score 0.0774) — an in-silico prediction, not a clinical call.

ARRDC3 p.His103Tyr

c.307C>T · VCV3949023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0774 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00622%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0774	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.20	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 0.9	GERP -3.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 12 kb · p 4.7e-08 · regional, not allelic
Overall
CADD	13.54	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00622% European (non-Finnish) · 73/1,173,284 alleles

Filtering AF 0.00506% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00465%

Overall 0.0047% 75/1,596,662 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00622%	16,072
Remaining individualsnot grpmax-eligible	0.00162%	61,788
South Asian	0.00115%	86,788

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.His103Tyr
Coding: c.307C>T
MANE Select: NM_020801
Type: single nucleotide variant
Location: chr5:91378749 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.36 · 3 PDB
Residue 103: 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.Arg43Ser 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-his103tyr (accessed [today's date]).

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