Is PLAA p.Pro479Leu (c.1436C>T) pathogenic?

PLAA p.Pro479Leu (c.1436C>T) is classified Uncertain significance in PLAA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). AlphaMissense: ambiguous (0.5443); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with PLAA p.Pro479Leu (c.1436C>T)?

PLAA p.Pro479Leu (c.1436C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PLAA p.Pro479Leu (c.1436C>T) in the general population?

PLAA p.Pro479Leu (c.1436C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about PLAA p.Pro479Leu (c.1436C>T)?

AlphaMissense predicts ambiguous (score 0.5443) — an in-silico prediction, not a clinical call.

PLAA p.Pro479Leu

c.1436C>T · rs1399400470 · VCV2233665

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5443 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5443	ambiguous
REVEL	0.385	indeterminate
SaProt	LLR -12.79	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing
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	28.5	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

Grpmax group 0.00134% African / African-American · 1/74,894 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00062% 10/1,613,696 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,894
South Asian	0.0011%	91,070
European (non-Finnish)	0.000678%	147,478

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.Pro479Leu
Coding: c.1436C>T
MANE Select: NM_001031689
dbSNP: rs1399400470
Type: single nucleotide variant
Location: chr9:26917147 (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.Pro479= Likely benign ★ 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-pro479leu (accessed [today's date]).

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