Is PLAA p.Asp100Glu (c.300C>A) pathogenic?

PLAA p.Asp100Glu (c.300C>A) is classified Likely benign in PLAA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: likely benign (0.1082); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with PLAA p.Asp100Glu (c.300C>A)?

PLAA p.Asp100Glu (c.300C>A) is associated with Inborn genetic diseases (ClinVar).

How common is PLAA p.Asp100Glu (c.300C>A) in the general population?

PLAA p.Asp100Glu (c.300C>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about PLAA p.Asp100Glu (c.300C>A)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

PLAA p.Asp100Glu

c.300C>A · VCV3307237

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.003	GERP -1.9, phastCons 0.55
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.094 · regional, not allelic
Overall
CADD	15.44	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 0.0165% Middle Eastern · 1/6,074 alleles

Filtering AF 0.0024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00261% 42/1,608,674 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,074
European (non-Finnish)	0.00323%	31,004
African / African-American	0.00268%	37,335
Remaining individualsnot grpmax-eligible	0.0016%	62,308

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.Asp100Glu
Coding: c.300C>A
MANE Select: NM_001031689
Type: single nucleotide variant
Location: chr9:26935056 (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

Disease context

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

Similar variants

PLAA p.Asp100Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
PLAA p.Ala271Val Uncertain significance ★★ ⚠ same condition
PLAA p.Arg268Gln Uncertain significance ★★ ⚠ same condition
PLAA p.Arg373Thr Uncertain significance ★★ ⚠ same condition
PLAA p.Arg499Cys Uncertain significance ★★ same condition
PLAA p.Arg7Ser Uncertain significance ★★ ⚠ same condition
PLAA p.Asn410Ser Uncertain significance ★★ ⚠ same condition
PLAA p.Asn520Ser 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/plaa-p-asp100glu (accessed [today's date]).

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