Is ARSF p.Pro388Arg (c.1163C>G) pathogenic?

ARSF p.Pro388Arg (c.1163C>G) is classified Uncertain significance in ARSF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely benign (0.1835); Absent from gnomAD v4.1.

How common is ARSF p.Pro388Arg (c.1163C>G) in the general population?

ARSF p.Pro388Arg (c.1163C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARSF p.Pro388Arg (c.1163C>G)?

AlphaMissense predicts likely benign (score 0.1835) — an in-silico prediction, not a clinical call.

ARSF p.Pro388Arg

c.1163C>G · rs2518527235 · VCV2269224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1835 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1835	likely benign
REVEL	0.801	moderately pathogenic-leaning
SaProt	LLR -11.68	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.5, phastCons 0.97
Regional constraint	o/e 1.04	unconstrained · MANE · 44 kb · p 0.34 · regional, not allelic
Overall
CADD	21.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARSF
Protein: p.Pro388Arg
Coding: c.1163C>G
MANE Select: NM_001201539
dbSNP: rs2518527235
Type: single nucleotide variant
Location: chrX:3103822 (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.Ala84Pro Uncertain significance ★ ⚠ same type
ARSF p.Arg103Cys Uncertain significance ★ ⚠ same type
ARSF p.Arg179His 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-pro388arg (accessed [today's date]).

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