Is GP9 p.Ser142Phe (c.425C>T) pathogenic?

GP9 p.Ser142Phe (c.425C>T) is classified Uncertain significance in GP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.175); Very rare (popmax 0.00673%, afr); Associated with Inborn genetic diseases.

What condition is associated with GP9 p.Ser142Phe (c.425C>T)?

GP9 p.Ser142Phe (c.425C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GP9 p.Ser142Phe (c.425C>T) in the general population?

GP9 p.Ser142Phe (c.425C>T) is very rare (popmax 0.00673%, afr) (gnomAD).

What do computational predictors say about GP9 p.Ser142Phe (c.425C>T)?

AlphaMissense predicts likely benign (score 0.175) — an in-silico prediction, not a clinical call.

GP9 p.Ser142Phe

c.425C>T · VCV4265277

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.175 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00673%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.175	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.23, phastCons 0.06
Regional constraint	o/e 0.94	unconstrained · MANE · 530 bp · p 0.38 · regional, not allelic
Overall
CADD	16.36	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00673% African / African-American · 5/74,302 alleles

Filtering AF 0.00257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00163%

Overall 0.00095% 15/1,579,522 alleles · very rare exomes 12/1,427,270 · genomes 3/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00673%	14,860
Remaining individualsnot grpmax-eligible	0.00163%	61,236
European (non-Finnish)	0.000771%	129,656

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: GP9
Protein: p.Ser142Phe
Coding: c.425C>T
MANE Select: NM_000174
Type: single nucleotide variant
Location: chr3:129062164 (GRCh38)
Structure: AlphaFold pLDDT 84.43 · 2 PDB

Full GP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GP9 p.Ala51Asp Uncertain significance ★★ ⚠ same condition
GP9 p.Arg52Cys Uncertain significance ★★ ⚠ same condition
GP9 p.Asp81Asn Uncertain significance ★★ ⚠ same condition
GP9 p.Gly129Ser Uncertain significance ★★ ⚠ same condition
GP9 p.Gly167Ser Uncertain significance ★★ ⚠ same condition
GP9 p.Gly42Arg Uncertain significance ★★ ⚠ same condition
GP9 p.Ala141Val Uncertain significance ★ ⚠ same condition
GP9 p.Ala158Asp Uncertain significance ★ ⚠ same condition

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/gp9-p-ser142phe (accessed [today's date]).

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