Is ARF3 p.Ala112Val (c.335C>T) pathogenic?

ARF3 p.Ala112Val (c.335C>T) is classified Uncertain significance in ARF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-04). AlphaMissense: ambiguous (0.4014); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with ARF3 p.Ala112Val (c.335C>T)?

ARF3 p.Ala112Val (c.335C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARF3 p.Ala112Val (c.335C>T) in the general population?

ARF3 p.Ala112Val (c.335C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ARF3 p.Ala112Val (c.335C>T)?

AlphaMissense predicts ambiguous (score 0.4014) — an in-silico prediction, not a clinical call.

ARF3 p.Ala112Val

c.335C>T · VCV3420238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4014 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4014	ambiguous
REVEL	0.327	indeterminate
SaProt	LLR -10.34	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 814 bp · p 5.9e-10 · regional, not allelic
Overall
CADD	27.5	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 0.00223% East Asian · 1/44,884 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,614,066 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
South Asian	0.0011%	91,078
European (non-Finnish)	0.000508%	196,669

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: ARF3
Protein: p.Ala112Val
Coding: c.335C>T
MANE Select: NM_001659
Type: single nucleotide variant
Location: chr12:48939704 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.23 · 2 PDB

Full ARF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARF3 p.Ala125Val Uncertain significance ★ ⚠ same condition
ARF3 p.Ala136Thr Uncertain significance ★ ⚠ same condition
ARF3 p.Arg117Gln Uncertain significance ★ ⚠ same condition
ARF3 p.Asn175Ser Uncertain significance ★ ⚠ same condition
ARF3 p.Gly50Val Uncertain significance ★ ⚠ same condition
ARF3 p.Ile13Val Uncertain significance ★ ⚠ same condition
ARF3 p.Leu170Pro Uncertain significance ★ ⚠ same condition
ARF3 p.Asp93Asn Pathogenic/Likely pathogenic ★★ 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/arf3-p-ala112val (accessed [today's date]).

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