Is PYROXD1 p.Asn416fs (c.1247_1250del) pathogenic?

PYROXD1 p.Asn416fs (c.12471250del) is classified Likely pathogenic in PYROXD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-23). No gnomAD frequency available for this variant.

How common is PYROXD1 p.Asn416fs (c.1247_1250del) in the general population?

PYROXD1 p.Asn416fs (c.1247_1250del) is no gnomAD frequency available for this variant (gnomAD).

PYROXD1 p.Asn416fs

c.1247_1250del · rs1942824066 · VCV987046

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (11 of 12, 9 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PYROXD1
Protein: p.Asn416fs
Coding: c.1247_1250del
MANE Select: NM_024854
dbSNP: rs1942824066
Type: Deletion
Location: chr12:21467609 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 2 PDB
Residue 416: a β-strand

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

Similar variants

PYROXD1 p.Cys111fs Pathogenic/Likely pathogenic ★★ same type
PYROXD1 p.Val298fs Pathogenic/Likely pathogenic ★★ same type
RECQL p.Arg644_Lys645del Uncertain significance ★★ same type
RECQL p.Lys643del Uncertain significance ★★ same type
RECQL p.Thr566del Uncertain significance ★★ same type
RECQL c.1797+14_1797+17del Benign/Likely benign ★★ same type
RECQL c.1798-5del Benign ★★ same type
PYROXD1 c.1254+1del Likely pathogenic ★ 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-asn416fs (accessed [today's date]).

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