Is PLAA p.Gln656Glu (c.1966C>G) pathogenic?

PLAA p.Gln656Glu (c.1966C>G) is classified Uncertain significance in PLAA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-22). AlphaMissense: likely benign (0.2986); Absent from gnomAD v4.1.

How common is PLAA p.Gln656Glu (c.1966C>G) in the general population?

PLAA p.Gln656Glu (c.1966C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLAA p.Gln656Glu (c.1966C>G)?

AlphaMissense predicts likely benign (score 0.2986) — an in-silico prediction, not a clinical call.

PLAA p.Gln656Glu

c.1966C>G · rs1824221487 · VCV2009457

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2986	likely benign
REVEL	0.444	indeterminate
SaProt	LLR -12.05	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.094 · regional, not allelic
Overall
CADD	26.5	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.Gln656Glu
Coding: c.1966C>G
MANE Select: NM_001031689
dbSNP: rs1824221487
Type: single nucleotide variant
Location: chr9:26905933 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB
Residue 656: an α-helix; the pul domain

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-gln656glu (accessed [today's date]).

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