Is ARSK p.Phe151Ser (c.452T>C) pathogenic?

ARSK p.Phe151Ser (c.452T>C) is classified Uncertain significance in ARSK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely pathogenic (0.8258); Very rare (popmax 0.00891%, eas).

How common is ARSK p.Phe151Ser (c.452T>C) in the general population?

ARSK p.Phe151Ser (c.452T>C) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about ARSK p.Phe151Ser (c.452T>C)?

AlphaMissense predicts likely pathogenic (score 0.8258) — an in-silico prediction, not a clinical call.

ARSK p.Phe151Ser

c.452T>C · VCV3316651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8258 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8258	likely pathogenic
REVEL	0.887	moderately pathogenic-leaning
SaProt	LLR -4.94	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.24 · regional, not allelic
Overall
CADD	27.6	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 0.00891% East Asian · 4/44,876 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00031% 5/1,612,094 alleles · very rare exomes 4/1,459,884 · genomes 1/152,210 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,219
European (non-Finnish)	8.48e-05%	1,178,724

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: ARSK
Protein: p.Phe151Ser
Coding: c.452T>C
MANE Select: NM_198150
Type: single nucleotide variant
Location: chr5:95582951 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.50

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

Similar variants

ARSK p.Lys518= Benign/Likely benign ★★ same type
ARSK p.Ala11Thr Uncertain significance ★ ⚠ same type
ARSK p.Ala191Pro Uncertain significance ★ ⚠ same type
ARSK p.Ala238Asp Uncertain significance ★ ⚠ same type
ARSK p.Ala318Thr Uncertain significance ★ ⚠ same type
ARSK p.Ala428Gly Uncertain significance ★ ⚠ same type
ARSK p.Arg122Gln Uncertain significance ★ ⚠ same type
ARSK p.Arg141Leu 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/arsk-p-phe151ser (accessed [today's date]).

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