Is PRKN p.Ala91Val (c.272C>T) pathogenic?

PRKN p.Ala91Val (c.272C>T) is classified Uncertain significance in PRKN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-16). AlphaMissense: likely benign (0.0753); Ultra-rare (popmax 0.0134%, afr); Associated with Inborn genetic diseases.

What condition is associated with PRKN p.Ala91Val (c.272C>T)?

PRKN p.Ala91Val (c.272C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRKN p.Ala91Val (c.272C>T) in the general population?

PRKN p.Ala91Val (c.272C>T) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

What do computational predictors say about PRKN p.Ala91Val (c.272C>T)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

PRKN p.Ala91Val

c.272C>T · rs528661586 · VCV1505064

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -7.05	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 0.53	GERP -2.6
Regional constraint	o/e 1.10	unconstrained · MANE · 1,378 kb · p 0.013 · regional, not allelic
Overall
CADD	9.613	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% African / African-American · 10/74,856 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00248% 40/1,613,430 alleles · ultra-rare exomes 34/1,461,668 · genomes 6/151,762 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,486
East Asian	0.00223%	44,854
European (non-Finnish)	0.0022%	45,383
Admixed American	0.00167%	59,940
Remaining individualsnot grpmax-eligible	0.0016%	62,498
South Asian	0.0011%	91,068

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: PRKN
Protein: p.Ala91Val
Coding: c.272C>T
MANE Select: NM_004562
dbSNP: rs528661586
Type: single nucleotide variant
Location: chr6:162262665 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.10 · 21 PDB
Residue 91: the 'necessary for pink1-dependent localization to mitochondria' region; the 'disordered' region

Full PRKN 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

PRKN p.Ala91Thr Likely benign ★ same residue
PRKN p.Ala91= Likely benign ★ same residue
PRKN p.Arg191Gln Uncertain significance ★★ ⚠ same condition
PRKN p.Arg191Trp Uncertain significance ★★ ⚠ same condition
PRKN p.Arg234Trp Uncertain significance ★★ ⚠ same condition
PRKN p.Arg97Gln Uncertain significance ★★ ⚠ same condition
PRKN p.Asp39Glu Uncertain significance ★★ ⚠ same condition
PRKN p.Cys268Ser 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/prkn-p-ala91val (accessed [today's date]).

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