Is ART4 p.Gln65Arg (c.194A>G) pathogenic?

ART4 p.Gln65Arg (c.194A>G) is classified Uncertain significance in ART4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-17). AlphaMissense: likely benign (0.2072); Ultra-rare (popmax 0.0176%, afr).

How common is ART4 p.Gln65Arg (c.194A>G) in the general population?

ART4 p.Gln65Arg (c.194A>G) is ultra-rare (popmax 0.0176%, afr) (gnomAD).

What do computational predictors say about ART4 p.Gln65Arg (c.194A>G)?

AlphaMissense predicts likely benign (score 0.2072) — an in-silico prediction, not a clinical call.

ART4 p.Gln65Arg

c.194A>G · VCV3433100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2072	likely benign
REVEL	0.327	indeterminate
SaProt	LLR -12.61	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 5.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.58 · regional, not allelic
Overall
CADD	24.0	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 0.0176% African / African-American · 13/73,938 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00822%

Overall 0.000877% 14/1,596,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0176%	5,688
European (non-Finnish)	8.52e-05%	1,174,226

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: ART4
Protein: p.Gln65Arg
Coding: c.194A>G
MANE Select: NM_021071
Type: single nucleotide variant
Location: chr12:14841104 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00

Full ART4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ART4 p.Ala103Val Uncertain significance ★ ⚠ same type
ART4 p.Ala20Ser Uncertain significance ★ ⚠ same type
ART4 p.Ala50Thr Uncertain significance ★ ⚠ same type
ART4 p.Ala58Thr Uncertain significance ★ ⚠ same type
ART4 p.Arg171Lys Uncertain significance ★ ⚠ same type
ART4 p.Arg171Thr Uncertain significance ★ ⚠ same type
ART4 p.Arg263Gly Uncertain significance ★ ⚠ same type
ART4 p.Asn257Ser 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/art4-p-gln65arg (accessed [today's date]).

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