Is PLAA p.Asp100Tyr (c.298G>T) pathogenic?

PLAA p.Asp100Tyr (c.298G>T) is classified Conflicting classifications of pathogenicity in PLAA (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.2105); Rare (popmax 0.284%, amr).

How common is PLAA p.Asp100Tyr (c.298G>T) in the general population?

PLAA p.Asp100Tyr (c.298G>T) is rare (popmax 0.284%, amr) (gnomAD).

What do computational predictors say about PLAA p.Asp100Tyr (c.298G>T)?

AlphaMissense predicts likely benign (score 0.2105) — an in-silico prediction, not a clinical call.

PLAA p.Asp100Tyr

c.298G>T · rs201814139 · VCV1551696

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2105 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.284%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2105	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -10.27	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 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.094 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.284% Admixed American · 167/58,714 alleles

Filtering AF 0.249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.236%

Overall 0.0107% 172/1,608,694 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.284%	352
Remaining individualsnot grpmax-eligible	0.00802%	12,468

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PLAA
Protein: p.Asp100Tyr
Coding: c.298G>T
MANE Select: NM_001031689
dbSNP: rs201814139
Type: single nucleotide variant
Location: chr9:26935058 (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.Asp100Glu Likely benign ★ same residue
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

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-asp100tyr (accessed [today's date]).

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