Is PCLAF p.Pro52Ala (c.154C>G) pathogenic?

PCLAF p.Pro52Ala (c.154C>G) is classified Uncertain significance in PCLAF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.127); Absent from gnomAD v4.1.

How common is PCLAF p.Pro52Ala (c.154C>G) in the general population?

PCLAF p.Pro52Ala (c.154C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PCLAF p.Pro52Ala (c.154C>G)?

AlphaMissense predicts likely benign (score 0.127) — an in-silico prediction, not a clinical call.

PCLAF p.Pro52Ala

c.154C>G · VCV3415748

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.127 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.127	likely benign
REVEL	0.287	benign-leaning
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 15 kb · p 0.19 · regional, not allelic
Overall
CADD	23.4	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

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: PCLAF
Protein: p.Pro52Ala
Coding: c.154C>G
MANE Select: NM_014736
Type: single nucleotide variant
Location: chr15:64376879 (GRCh38)
Gene constraint: LOEUF 1.127 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.67 · 4 PDB
Residue 52: the 'disordered' region; an α-helix

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

Similar variants

PCLAF p.Pro52Thr Uncertain significance ★ ⚠ same residue
PCLAF p.Arg41Lys Uncertain significance ★ ⚠ same type
PCLAF p.Arg56Cys Uncertain significance ★ same type
PCLAF p.Asp75Val Uncertain significance ★ ⚠ same type
PCLAF p.Lys24Arg Uncertain significance ★ ⚠ same type
PCLAF p.Lys46Thr Uncertain significance ★ same type
PCLAF p.Lys97Glu Uncertain significance ★ ⚠ same type
PCLAF p.Pro22Leu 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/pclaf-p-pro52ala (accessed [today's date]).

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