Is GNPAT p.Ser26Pro (c.76T>C) pathogenic?

GNPAT p.Ser26Pro (c.76T>C) is classified Uncertain significance in GNPAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.0654); Very rare (popmax 0.00842%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GNPAT p.Ser26Pro (c.76T>C)?

GNPAT p.Ser26Pro (c.76T>C) is associated with Inborn genetic diseases (ClinVar).

How common is GNPAT p.Ser26Pro (c.76T>C) in the general population?

GNPAT p.Ser26Pro (c.76T>C) is very rare (popmax 0.00842%, nfe) (gnomAD).

What do computational predictors say about GNPAT p.Ser26Pro (c.76T>C)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

GNPAT p.Ser26Pro

c.76T>C · VCV3521014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00842%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -5.70	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 3.1	GERP -1.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 36 kb · p 0.00057 · regional, not allelic
Overall
CADD	19.02	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 0.00842% European (non-Finnish) · 99/1,175,894 alleles

Filtering AF 0.00705% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00654%

Overall 0.0064% 103/1,609,290 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00842%	11,878
Remaining individualsnot grpmax-eligible	0.00481%	20,772
African / African-American	0.00134%	74,810

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: GNPAT
Protein: p.Ser26Pro
Coding: c.76T>C
MANE Select: NM_014236
Type: single nucleotide variant
Location: chr1:231241454 (GRCh38)
Gene constraint: LOEUF 0.572 · pLI 0.88 (gnomAD)
Structure: AlphaFold pLDDT 88.96

Full GNPAT 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

GNPAT p.Ala206Ser Uncertain significance ★★ ⚠ same condition
GNPAT p.Arg115His Uncertain significance ★★ ⚠ same condition
GNPAT p.Arg202Gln Uncertain significance ★★ ⚠ same condition
GNPAT p.Arg515Cys Uncertain significance ★★ ⚠ same condition
GNPAT p.Arg515His Uncertain significance ★★ ⚠ same condition
GNPAT p.Arg518His Uncertain significance ★★ ⚠ same condition
GNPAT p.Asp190Glu Uncertain significance ★★ ⚠ same condition
GNPAT p.Cys122Tyr 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/gnpat-p-ser26pro (accessed [today's date]).

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