Is PDLIM5 p.Pro88Ser (c.262C>T) pathogenic?

PDLIM5 p.Pro88Ser (c.262C>T) is classified Uncertain significance in PDLIM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0703); Ultra-rare (popmax 0.0167%, amr).

How common is PDLIM5 p.Pro88Ser (c.262C>T) in the general population?

PDLIM5 p.Pro88Ser (c.262C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about PDLIM5 p.Pro88Ser (c.262C>T)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

PDLIM5 p.Pro88Ser

c.262C>T · VCV3930403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -7.61	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 -0.03	GERP -3.1, phastCons 0.008
Regional constraint	o/e 0.93	unconstrained · MANE · 209 kb · p 0.062 · regional, not allelic
Overall
CADD	9.45	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 0.0167% Admixed American · 10/59,984 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00447% 72/1,612,448 alleles · ultra-rare exomes 62/1,460,554 · genomes 10/151,894 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,998
Middle Eastern	0.0165%	6,056
Remaining individualsnot grpmax-eligible	0.0144%	6,940
South Asian	0.00769%	13,001
European (non-Finnish)	0.00373%	26,796
Finnishnot grpmax-eligible	0.00157%	63,664

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: PDLIM5
Protein: p.Pro88Ser
Coding: c.262C>T
MANE Select: NM_006457
Type: single nucleotide variant
Location: chr4:94573364 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.95 · 3 PDB

Full PDLIM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDLIM5 p.Ala155= Benign ★★ same type
PDLIM5 p.Tyr557Cys Likely benign ★★ ⚠ same type
PDLIM5 p.Ala155Val Uncertain significance ★ ⚠ same type
PDLIM5 p.Ala187Val Uncertain significance ★ ⚠ same type
PDLIM5 p.Ala196Thr Uncertain significance ★ ⚠ same type
PDLIM5 p.Ala200Glu Uncertain significance ★ ⚠ same type
PDLIM5 p.Ala317Gly Uncertain significance ★ ⚠ same type
PDLIM5 p.Ala476Val 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/pdlim5-p-pro88ser (accessed [today's date]).

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