Is ALPG p.Trp267Cys (c.801G>T) pathogenic?

ALPG p.Trp267Cys (c.801G>T) is classified Uncertain significance in ALPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely pathogenic (0.8373); Absent from gnomAD v4.1.

How common is ALPG p.Trp267Cys (c.801G>T) in the general population?

ALPG p.Trp267Cys (c.801G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALPG p.Trp267Cys (c.801G>T)?

AlphaMissense predicts likely pathogenic (score 0.8373) — an in-silico prediction, not a clinical call.

ALPG p.Trp267Cys

c.801G>T · VCV3858406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8373 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,580,192)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8373	likely pathogenic
REVEL	0.851	moderately pathogenic-leaning
SaProt	LLR -14.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.58, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 265 bp · p 6.5e-05 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,580,192). 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: ALPG
Protein: p.Trp267Cys
Coding: c.801G>T
MANE Select: NM_031313
Type: single nucleotide variant
Location: chr2:232408518 (GRCh38)
Gene constraint: LOEUF 1.103 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.31

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

Similar variants

ALPG p.Trp267Arg Uncertain significance ★ ⚠ same residue
ALPG p.Arg498Pro Benign ★★ same type
ALPG p.Gly230= Benign ★★ same type
ALPG p.Gly500Asp Likely benign ★★ same type
ALPG p.His172= Benign/Likely benign ★★ same type
ALPG p.Leu8= Benign ★★ same type
ALPG p.Pro228Arg Benign ★★ ⚠ same type
ALPG p.Pro94Ser Benign ★★ ⚠ 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/alpg-p-trp267cys (accessed [today's date]).

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