Is ARSF p.Ala411Pro (c.1231G>C) pathogenic?

ARSF p.Ala411Pro (c.1231G>C) is classified Uncertain significance in ARSF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-11). AlphaMissense: likely pathogenic (0.8174); Very rare (popmax 0.00101%, nfe).

How common is ARSF p.Ala411Pro (c.1231G>C) in the general population?

ARSF p.Ala411Pro (c.1231G>C) is very rare (popmax 0.00101%, nfe) (gnomAD).

What do computational predictors say about ARSF p.Ala411Pro (c.1231G>C)?

AlphaMissense predicts likely pathogenic (score 0.8174) — an in-silico prediction, not a clinical call.

ARSF p.Ala411Pro

c.1231G>C · VCV3787474

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8174 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00101%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8174	likely pathogenic
REVEL	0.467	indeterminate
SaProt	LLR -14.93	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -1.5, phastCons 0.017
Regional constraint	o/e 1.04	unconstrained · MANE · 44 kb · p 0.34 · regional, not allelic
Overall
CADD	12.89	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 0.00101% European (non-Finnish) · 9/895,057 alleles

Filtering AF 0.000473% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000343%

Overall 0.000744% 9/1,209,418 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.Ala411Pro
Coding: c.1231G>C
MANE Select: NM_001201539
Type: single nucleotide variant
Location: chrX:3103890 (GRCh38)
Structure: AlphaFold pLDDT 90.98

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

Similar variants

ARSF p.Ala411Thr Uncertain significance ★ ⚠ same residue
ARSF c.1102+5G>A Likely benign ★★ same type
ARSF p.Pro6= Benign ★★ same type
ARSF p.Ala112Ser Uncertain significance ★ ⚠ same type
ARSF p.Ala84Pro 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-ala411pro (accessed [today's date]).

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