Is PYROXD1 p.Asn155= (c.465C>T) pathogenic?

PYROXD1 p.Asn155= (c.465C>T) is classified Likely benign in PYROXD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). Very rare (popmax 0.00327%, nfe).

How common is PYROXD1 p.Asn155= (c.465C>T) in the general population?

PYROXD1 p.Asn155= (c.465C>T) is very rare (popmax 0.00327%, nfe) (gnomAD).

PYROXD1 p.Asn155=

c.465C>T · rs748976919 · VCV1548176

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00327%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.58 · evaluated, not missing
Pangolin	Δ0.24	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -1.8	GERP -3.2
Overall
CADD	7.654	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00327% European (non-Finnish) · 38/1,163,238 alleles

Filtering AF 0.00243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00213%

Overall 0.00291% 46/1,581,696 alleles · very rare exomes 44/1,429,778 · genomes 2/151,918 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00981%	10,194
European (non-Finnish)grpmax	0.00327%	30,612
African / African-American	0.00271%	36,861

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PYROXD1
Protein: p.Asn155=
Coding: c.465C>T
MANE Select: NM_024854
dbSNP: rs748976919
Type: single nucleotide variant
Location: chr12:21452131 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 2 PDB
Residue 155: a UniProt-annotated variant site (in mfm8; also found in a patient with limb-girdle muscular dystrophy; decreased nadph dehydrogenase activity; decreased function in cellular response to oxidative stress; no effect on subcellular location in the nucleus and sarcomere)

Full PYROXD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PYROXD1 p.Asn155Ser Pathogenic ★★ same residue
PYROXD1 c.285+1G>A Pathogenic/Likely pathogenic ★★ same type
PYROXD1 c.881-2A>T Likely pathogenic ★★ same type
PYROXD1 p.Ala393Val Uncertain significance ★★ ⚠ same type
PYROXD1 p.Arg132Cys Uncertain significance ★★ ⚠ same type
PYROXD1 p.Arg455Gln Uncertain significance ★★ ⚠ same type
PYROXD1 p.Arg76Cys Uncertain significance ★★ ⚠ same type
PYROXD1 p.Asn52Asp 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/pyroxd1-p-asn155 (accessed [today's date]).

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