Is PIGN p.Val898Phe (c.2692G>T) pathogenic?

PIGN p.Val898Phe (c.2692G>T) is classified Uncertain significance in PIGN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely pathogenic (0.5965); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PIGN p.Val898Phe (c.2692G>T)?

PIGN p.Val898Phe (c.2692G>T) is associated with Inborn genetic diseases (ClinVar).

How common is PIGN p.Val898Phe (c.2692G>T) in the general population?

PIGN p.Val898Phe (c.2692G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PIGN p.Val898Phe (c.2692G>T)?

AlphaMissense predicts likely pathogenic (score 0.5965) — an in-silico prediction, not a clinical call.

PIGN p.Val898Phe

c.2692G>T · rs2511678154 · VCV3212811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5965 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5965	likely pathogenic
REVEL	0.23	benign-leaning
SaProt	LLR -14.32	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 109 kb · p 0.83 · regional, not allelic
Overall
CADD	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PIGN
Protein: p.Val898Phe
Coding: c.2692G>T
MANE Select: NM_176787
dbSNP: rs2511678154
Type: single nucleotide variant
Location: chr18:62045960 (GRCh38)
Gene constraint: LOEUF 1.46 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.33

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIGN p.Val898Ala Uncertain significance ★ ⚠ same residue
PIGN c.1675-1G>T Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Arg613Ter Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Arg785His Likely pathogenic ★★ same condition
PIGN p.Arg95Trp Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Leu311Trp Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Ala100Thr Uncertain significance ★★ ⚠ same condition
PIGN p.Ala805Thr 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/pign-p-val898phe (accessed [today's date]).

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