Is ARF4 p.Arg97His (c.290G>A) pathogenic?

ARF4 p.Arg97His (c.290G>A) is classified Uncertain significance in ARF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely benign (0.1836); Ultra-rare (popmax 0.0246%, eas).

How common is ARF4 p.Arg97His (c.290G>A) in the general population?

ARF4 p.Arg97His (c.290G>A) is ultra-rare (popmax 0.0246%, eas) (gnomAD).

What do computational predictors say about ARF4 p.Arg97His (c.290G>A)?

AlphaMissense predicts likely benign (score 0.1836) — an in-silico prediction, not a clinical call.

ARF4 p.Arg97His

c.290G>A · rs748489377 · VCV2462602

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1836 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0246%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1836	likely benign
REVEL	0.471	indeterminate
SaProt	LLR -12.58	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.96, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 25 kb · p 3.8e-13 · regional, not allelic
Overall
CADD	25.9	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 0.0246% East Asian · 11/44,750 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00304% 49/1,613,536 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0246%	4,068
Middle Eastern	0.0165%	6,056
European (non-Finnish)	0.00288%	34,701
Admixed American	0.00167%	59,948
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00133%	75,010

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: ARF4
Protein: p.Arg97His
Coding: c.290G>A
MANE Select: NM_001660
dbSNP: rs748489377
Type: single nucleotide variant
Location: chr3:57577356 (GRCh38)
Gene constraint: LOEUF 0.418 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.89 · 1 PDB
Residue 97: an α-helix

Full ARF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARF4 p.Arg97Ser Uncertain significance ★ ⚠ same residue
ARF4 p.Arg149Pro Uncertain significance ★ ⚠ same type
ARF4 p.Gly14Val Uncertain significance ★ ⚠ same type
ARF4 p.Ile61Val Uncertain significance ★ ⚠ same type
ARF4 p.Leu88Val Uncertain significance ★ ⚠ same type
ARF4 p.Lys16Arg Uncertain significance ★ ⚠ same type
ARF4 p.Thr164Asn 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/arf4-p-arg97his (accessed [today's date]).

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