Is ARAF p.Ala110Val (c.329C>T) pathogenic?

ARAF p.Ala110Val (c.329C>T) is classified Uncertain significance in ARAF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.1725); Very rare (popmax 0.00592%, eas).

How common is ARAF p.Ala110Val (c.329C>T) in the general population?

ARAF p.Ala110Val (c.329C>T) is very rare (popmax 0.00592%, eas) (gnomAD).

What do computational predictors say about ARAF p.Ala110Val (c.329C>T)?

AlphaMissense predicts likely benign (score 0.1725) — an in-silico prediction, not a clinical call.

ARAF p.Ala110Val

c.329C>T · rs779648831 · VCV3128183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00592%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1725	likely benign
REVEL	0.36	indeterminate
SaProt	LLR -8.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	phastCons 0.078
Regional constraint	o/e 0.29	constrained · MANE · 309 bp · p 3.5e-08 · regional, not allelic
Overall
CADD	20.3	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 0.00592% East Asian · 2/33,761 alleles

Filtering AF 0.000981% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000826% 10/1,210,226 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00592%	16,880
Admixed American	0.00218%	45,816
South Asian	0.00176%	56,867
African / African-American	0.00175%	57,201
European (non-Finnish)	0.000558%	179,053

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: ARAF
Protein: p.Ala110Val
Coding: c.329C>T
MANE Select: NM_001654
dbSNP: rs779648831
Type: single nucleotide variant
Location: chrX:47565010 (GRCh38)
Structure: AlphaFold pLDDT 70.99 · 7 PDB

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

Similar variants

ARAF p.His191Tyr Uncertain significance ★★ ⚠ same type
ARAF p.Ala334= Benign ★★ same type
ARAF p.Leu471= Benign ★★ same type
ARAF c.97-7C>T Uncertain significance ★ same type
ARAF p.Ala261Val Uncertain significance ★ ⚠ same type
ARAF p.Ala48Pro Uncertain significance ★ ⚠ same type
ARAF p.Arg151Cys Uncertain significance ★ ⚠ same type
ARAF p.Arg166Ser 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/araf-p-ala110val (accessed [today's date]).

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