Is GPAM p.Pro635Ser (c.1903C>T) pathogenic?

GPAM p.Pro635Ser (c.1903C>T) is classified Uncertain significance in GPAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely pathogenic (0.6385); Absent from gnomAD v4.1.

How common is GPAM p.Pro635Ser (c.1903C>T) in the general population?

GPAM p.Pro635Ser (c.1903C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GPAM p.Pro635Ser (c.1903C>T)?

AlphaMissense predicts likely pathogenic (score 0.6385) — an in-silico prediction, not a clinical call.

GPAM p.Pro635Ser

c.1903C>T · VCV4031055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6385 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,579,744)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6385	likely pathogenic
REVEL	0.699	pathogenic-leaning
SaProt	LLR -8.39	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 28 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,579,744). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GPAM
Protein: p.Pro635Ser
Coding: c.1903C>T
MANE Select: NM_001244949
Type: single nucleotide variant
Location: chr10:112158393 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 2 PDB
Residue 635: a β-strand

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

Similar variants

GPAM p.Ala420Val Benign ★★ same type
GPAM p.Asp399= Benign ★★ same type
GPAM p.Ile43Val Benign ★★ same type
GPAM c.102+1G>A Uncertain significance ★ same type
GPAM p.Ala144Thr Uncertain significance ★ ⚠ same type
GPAM p.Ala144Val Uncertain significance ★ ⚠ same type
GPAM p.Ala327Thr Uncertain significance ★ ⚠ same type
GPAM p.Ala382Thr 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/gpam-p-pro635ser (accessed [today's date]).

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