Is GSS p.Pro358Arg (c.1073C>G) pathogenic?

GSS p.Pro358Arg (c.1073C>G) is classified Uncertain significance in GSS (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-14). AlphaMissense: ambiguous (0.4887); Absent from gnomAD v4.1.

How common is GSS p.Pro358Arg (c.1073C>G) in the general population?

GSS p.Pro358Arg (c.1073C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GSS p.Pro358Arg (c.1073C>G)?

AlphaMissense predicts ambiguous (score 0.4887) — an in-silico prediction, not a clinical call.

GSS p.Pro358Arg

c.1073C>G · rs752295865 · VCV993376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4887 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4887	ambiguous
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -14.46	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 23 kb · p 8.1e-05 · regional, not allelic
Overall
CADD	29.7	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: GSS
Protein: p.Pro358Arg
Coding: c.1073C>G
MANE Select: NM_000178
dbSNP: rs752295865
Type: single nucleotide variant
Location: chr20:34931374 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.25 · 2 PDB
Residue 358: an α-helix

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

Similar variants

GSS c.129+1663A>G Pathogenic/Likely pathogenic ★★ same type
GSS c.130-1G>C Pathogenic/Likely pathogenic ★★ same type
GSS c.-9+5G>A Pathogenic ★★ same type
GSS p.Arg125Cys Pathogenic/Likely pathogenic ★★ same type
GSS p.Arg164Gln Pathogenic ★★ ⚠ same type
GSS p.Arg164Ter Pathogenic/Likely pathogenic ★★ same type
GSS p.Arg236Ter Pathogenic/Likely pathogenic ★★ same type
GSS p.Arg237Ter Pathogenic/Likely pathogenic ★★ 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/gss-p-pro358arg (accessed [today's date]).

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