Is GNPAT p.Phe365= (c.1095T>C) pathogenic?

GNPAT p.Phe365= (c.1095T>C) is classified Conflicting classifications of pathogenicity in GNPAT (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0763%, nfe); Associated with rhizomelic chondrodysplasia punctata type 2.

What condition is associated with GNPAT p.Phe365= (c.1095T>C)?

GNPAT p.Phe365= (c.1095T>C) is associated with rhizomelic chondrodysplasia punctata type 2 (ClinVar).

How common is GNPAT p.Phe365= (c.1095T>C) in the general population?

GNPAT p.Phe365= (c.1095T>C) is ultra-rare (popmax 0.0763%, nfe) (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

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

GNPAT p.Phe365=

c.1095T>C · rs139272614 · VCV875980

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0763%, nfe)

Conditions

rhizomelic chondrodysplasia punctata type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.052	GERP -1.2, phastCons 0.88
Overall
CADD	8.174	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0763% European (non-Finnish) · 898/1,177,374 alleles

Filtering AF 0.0721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0704%

Overall 0.0601% 968/1,611,282 alleles · ultra-rare exomes 912/1,458,972 · genomes 56/152,310 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0763%	1,311
Remaining individualsnot grpmax-eligible	0.0561%	1,783
Admixed American	0.035%	2,858
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,932
African / African-American	0.0107%	9,373

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.Phe365=
Coding: c.1095T>C
MANE Select: NM_014236
dbSNP: rs139272614
Type: single nucleotide variant
Location: chr1:231267719 (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 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
GNPAT c.-47C>A 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-phe365 (accessed [today's date]).

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