Is ARSF p.Ala84Pro (c.250G>C) pathogenic?

ARSF p.Ala84Pro (c.250G>C) is classified Uncertain significance in ARSF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-17). AlphaMissense: likely pathogenic (0.9663); Very rare (popmax 0.000447%, nfe).

How common is ARSF p.Ala84Pro (c.250G>C) in the general population?

ARSF p.Ala84Pro (c.250G>C) is very rare (popmax 0.000447%, nfe) (gnomAD).

What do computational predictors say about ARSF p.Ala84Pro (c.250G>C)?

AlphaMissense predicts likely pathogenic (score 0.9663) — an in-silico prediction, not a clinical call.

ARSF p.Ala84Pro

c.250G>C · VCV4839996

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000447%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9663	likely pathogenic · top 4% in ARSF
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -12.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 44 kb · p 0.34 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000447% European (non-Finnish) · 4/895,500 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000364% 4/1,097,863 alleles · very rare

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: ARSF
Protein: p.Ala84Pro
Coding: c.250G>C
MANE Select: NM_001201539
Type: single nucleotide variant
Location: chrX:3076636 (GRCh38)
Structure: AlphaFold pLDDT 90.98

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

Similar variants

ARSF c.1102+5G>A Likely benign ★★ same type
ARSF p.Pro6= Benign ★★ same type
ARSF p.Ala112Ser Uncertain significance ★ ⚠ same type
ARSF p.Ala411Pro Uncertain significance ★ ⚠ same type
ARSF p.Ala411Thr Uncertain significance ★ ⚠ same type
ARSF p.Arg103Cys Uncertain significance ★ ⚠ same type
ARSF p.Arg179His Uncertain significance ★ ⚠ same type
ARSF p.Arg249Leu 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/arsf-p-ala84pro (accessed [today's date]).

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