Is PCLO p.Pro511Ser (c.1531C>T) pathogenic?

PCLO p.Pro511Ser (c.1531C>T) is classified Likely benign in PCLO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). AlphaMissense: likely benign (0.0564); Very rare (popmax 0.0023%, eas); Associated with Inborn genetic diseases.

What condition is associated with PCLO p.Pro511Ser (c.1531C>T)?

PCLO p.Pro511Ser (c.1531C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCLO p.Pro511Ser (c.1531C>T) in the general population?

PCLO p.Pro511Ser (c.1531C>T) is very rare (popmax 0.0023%, eas) (gnomAD).

What do computational predictors say about PCLO p.Pro511Ser (c.1531C>T)?

AlphaMissense predicts likely benign (score 0.0564) — an in-silico prediction, not a clinical call.

PCLO p.Pro511Ser

c.1531C>T · VCV3305142

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0564 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0023%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0564	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -2.8
Regional constraint	o/e 1.05	unconstrained · MANE · 246 kb · p 0.0018 · regional, not allelic
Overall
CADD	0.001	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0023% East Asian · 1/43,442 alleles

Overall 0.00013% 2/1,538,776 alleles · very rare exomes 1/1,393,500 · genomes 1/145,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0023%	43,442
Admixed American	0.00186%	53,728

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: PCLO
Protein: p.Pro511Ser
Coding: c.1531C>T
MANE Select: NM_033026
Type: single nucleotide variant
Location: chr7:83155110 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Residue 511: the 'disordered' region; the '10 x 10 aa tandem approximate repeats of p-a-k-p-q-p-q-q-p-x' region

Full PCLO 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

PCLO p.Pro511Arg Uncertain significance ★ ⚠ same residue
PCLO p.Pro511= Likely benign ★ same residue
PCLO p.Ala1410Thr Uncertain significance ★★ ⚠ same condition
PCLO p.Ala2123Val Uncertain significance ★★ ⚠ same condition
PCLO p.Ala2259Gly Uncertain significance ★★ ⚠ same condition
PCLO p.Ala3066Ser Uncertain significance ★★ ⚠ same condition
PCLO p.Ala3613Ser Uncertain significance ★★ ⚠ same condition
PCLO p.Ala3662Thr 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/pclo-p-pro511ser (accessed [today's date]).

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