Is PLAA p.Ile159Phe (c.475A>T) pathogenic?

PLAA p.Ile159Phe (c.475A>T) is classified Uncertain significance in PLAA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: ambiguous (0.5153); Absent from gnomAD v4.1.

How common is PLAA p.Ile159Phe (c.475A>T) in the general population?

PLAA p.Ile159Phe (c.475A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLAA p.Ile159Phe (c.475A>T)?

AlphaMissense predicts ambiguous (score 0.5153) — an in-silico prediction, not a clinical call.

PLAA p.Ile159Phe

c.475A>T · rs2489209966 · VCV2014799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5153 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5153	ambiguous
REVEL	0.32	indeterminate
SaProt	LLR -6.09	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.094 · regional, not allelic
Overall
CADD	26.8	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: PLAA
Protein: p.Ile159Phe
Coding: c.475A>T
MANE Select: NM_001031689
dbSNP: rs2489209966
Type: single nucleotide variant
Location: chr9:26928190 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB

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

Similar variants

PLAA p.Arg524Ter Likely pathogenic ★★ same type
PLAA p.Ala156Val Uncertain significance ★★ ⚠ same type
PLAA p.Ala264Thr Uncertain significance ★★ ⚠ same type
PLAA p.Ala271Val Uncertain significance ★★ ⚠ same type
PLAA p.Arg268Gln Uncertain significance ★★ ⚠ same type
PLAA p.Arg373Thr Uncertain significance ★★ ⚠ same type
PLAA p.Arg499Cys Uncertain significance ★★ same type
PLAA p.Arg7Ser 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/plaa-p-ile159phe (accessed [today's date]).

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