Is PDLIM5 p.Pro441Arg (c.1322C>G) pathogenic?

PDLIM5 p.Pro441Arg (c.1322C>G) is classified Uncertain significance in PDLIM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely pathogenic (0.7821); Absent from gnomAD v4.1.

How common is PDLIM5 p.Pro441Arg (c.1322C>G) in the general population?

PDLIM5 p.Pro441Arg (c.1322C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDLIM5 p.Pro441Arg (c.1322C>G)?

AlphaMissense predicts likely pathogenic (score 0.7821) — an in-silico prediction, not a clinical call.

PDLIM5 p.Pro441Arg

c.1322C>G · rs2532193652 · VCV2488533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7821 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7821	likely pathogenic
REVEL	0.634	indeterminate
SaProt	LLR -14.14	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 209 kb · p 0.062 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDLIM5
Protein: p.Pro441Arg
Coding: c.1322C>G
MANE Select: NM_006457
dbSNP: rs2532193652
Type: single nucleotide variant
Location: chr4:94654498 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.95 · 3 PDB
Residue 441: the lim zinc-binding 1 domain; a turn

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-pro441arg (accessed [today's date]).

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