Is GNPAT p.Ser9Phe (c.26C>T) pathogenic?

GNPAT p.Ser9Phe (c.26C>T) is classified Benign in GNPAT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1086); Common (popmax 5.55%, afr) — too common for a highly-penetrant pathogenic allele; Associated with rhizomelic chondrodysplasia punctata type 2.

What condition is associated with GNPAT p.Ser9Phe (c.26C>T)?

GNPAT p.Ser9Phe (c.26C>T) is associated with rhizomelic chondrodysplasia punctata type 2 (ClinVar).

How is Rhizomelic chondrodysplasia punctata inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about GNPAT p.Ser9Phe (c.26C>T)?

AlphaMissense predicts likely benign (score 0.1086) — an in-silico prediction, not a clinical call.

GNPAT p.Ser9Phe

Q: How common is GNPAT p.Ser9Phe (c.26C>T) in the general population?

GNPAT p.Ser9Phe (c.26C>T) is common (popmax 5.55%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.26C>T · rs113480953 · VCV260361

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1086 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.55%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

rhizomelic chondrodysplasia punctata type 2

Computational evidence

Protein change
AlphaMissense	0.1086	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -8.53	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 0.048	GERP -2.9
Regional constraint	o/e 0.88	unconstrained · MANE · 36 kb · p 0.00057 · regional, not allelic
Overall
CADD	13.66	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

Grpmax group 5.55% African / African-American · 4,163/75,016 alleles

Filtering AF 5.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.35%

Overall 0.292% 4,719/1,613,988 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.55%	18
Admixed American	0.393%	254
Remaining individualsnot grpmax-eligible	0.362%	277
Middle Eastern	0.115%	866
South Asian	0.0253%	3,960
European (non-Finnish)	0.00534%	18,728
East Asian	0.00223%	44,882

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.Ser9Phe
Coding: c.26C>T
MANE Select: NM_014236
dbSNP: rs113480953
Type: single nucleotide variant
Location: chr1:231241404 (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

rhizomelic chondrodysplasia punctata type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Rhizomelic chondrodysplasia punctata (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GNPAT p.Ser9fs Likely pathogenic ★ same residue
GNPAT c.569-3T>G Pathogenic ★★ same condition
GNPAT p.Arg163Ter Pathogenic ★★ same condition
GNPAT p.Arg211Cys Likely pathogenic ★★ same condition
GNPAT p.Arg211His Pathogenic ★★ same condition
GNPAT p.Trp386Ter Pathogenic/Likely pathogenic ★★ same condition
GNPAT p.Tyr60Ter Pathogenic/Likely pathogenic ★★ same condition
GNPAT c.924+4C>T 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-ser9phe (accessed [today's date]).

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