Is ART4 p.Phe55Ser (c.164T>C) pathogenic?

ART4 p.Phe55Ser (c.164T>C) is classified Uncertain significance in ART4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). AlphaMissense: likely benign (0.1944); Rare (popmax 0.124%, afr).

How common is ART4 p.Phe55Ser (c.164T>C) in the general population?

ART4 p.Phe55Ser (c.164T>C) is rare (popmax 0.124%, afr) (gnomAD).

What do computational predictors say about ART4 p.Phe55Ser (c.164T>C)?

AlphaMissense predicts likely benign (score 0.1944) — an in-silico prediction, not a clinical call.

ART4 p.Phe55Ser

c.164T>C · rs140754622 · VCV3129959

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1944 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.124%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1944	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -11.41	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.58 · regional, not allelic
Overall
CADD	23.1	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 0.124% African / African-American · 90/72,544 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0956%

Overall 0.00585% 92/1,572,728 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.124%	806
Remaining individualsnot grpmax-eligible	0.0033%	30,258

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.Phe55Ser
Coding: c.164T>C
MANE Select: NM_021071
dbSNP: rs140754622
Type: single nucleotide variant
Location: chr12:14841134 (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.Phe55Leu Uncertain significance ★ ⚠ same residue
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

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-phe55ser (accessed [today's date]).

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