Is PCLO p.Pro481Ser (c.1441C>T) pathogenic?

PCLO p.Pro481Ser (c.1441C>T) is classified Uncertain significance in PCLO (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-05). AlphaMissense: likely benign (0.0604); Very rare (popmax 0.00119%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PCLO p.Pro481Ser (c.1441C>T)?

PCLO p.Pro481Ser (c.1441C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCLO p.Pro481Ser (c.1441C>T) in the general population?

PCLO p.Pro481Ser (c.1441C>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about PCLO p.Pro481Ser (c.1441C>T)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

PCLO p.Pro481Ser

c.1441C>T · rs865971917 · VCV1477277

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.015	strongly 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 -3.4	GERP -3.1
Regional constraint	o/e 1.05	unconstrained · MANE · 246 kb · p 0.0018 · regional, not allelic
Overall
CADD	0.031	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,226 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00087% 14/1,609,490 alleles · very rare exomes 12/1,460,736 · genomes 2/148,754 · joint denominator

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.Pro481Ser
Coding: c.1441C>T
MANE Select: NM_033026
dbSNP: rs865971917
Type: single nucleotide variant
Location: chr7:83155200 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Residue 481: 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.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
PCLO p.Ala3695Val Uncertain significance ★★ ⚠ same condition
PCLO p.Ala3811Gly 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-pro481ser (accessed [today's date]).

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