Is PLIN5 p.Ala232Val (c.695C>T) pathogenic?

PLIN5 p.Ala232Val (c.695C>T) is classified Uncertain significance in PLIN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1059); Ultra-rare (popmax 0.0453%, afr).

How common is PLIN5 p.Ala232Val (c.695C>T) in the general population?

PLIN5 p.Ala232Val (c.695C>T) is ultra-rare (popmax 0.0453%, afr) (gnomAD).

What do computational predictors say about PLIN5 p.Ala232Val (c.695C>T)?

AlphaMissense predicts likely benign (score 0.1059) — an in-silico prediction, not a clinical call.

PLIN5 p.Ala232Val

c.695C>T · VCV4569547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1059 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0453%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1059	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -7.45	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 2.4	GERP -0.58, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.045 · regional, not allelic
Overall
CADD	22.0	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 0.0453% African / African-American · 34/75,054 alleles

Filtering AF 0.0333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0291%

Overall 0.00242% 39/1,613,528 alleles · ultra-rare exomes 17/1,461,214 · genomes 22/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0453%	2,207
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	0.000169%	590,012

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: PLIN5
Protein: p.Ala232Val
Coding: c.695C>T
MANE Select: NM_001013706
Type: single nucleotide variant
Location: chr19:4525658 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.54
Residue 232: the 'interaction with pnpla2 and abhd5' region

Full PLIN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLIN5 p.Ala232Thr Uncertain significance ★ ⚠ same residue
PLIN5 p.Pro452Leu Uncertain significance ★★ ⚠ same type
PLIN5 p.Ala174Val Uncertain significance ★ ⚠ same type
PLIN5 p.Ala175Pro Uncertain significance ★ ⚠ same type
PLIN5 p.Ala310Thr Uncertain significance ★ ⚠ same type
PLIN5 p.Ala341Val Uncertain significance ★ ⚠ same type
PLIN5 p.Ala356Ser Uncertain significance ★ ⚠ same type
PLIN5 p.Ala356Thr 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/plin5-p-ala232val (accessed [today's date]).

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