Is PCLO p.Gly1663Glu (c.4988G>A) pathogenic?

PCLO p.Gly1663Glu (c.4988G>A) is classified Uncertain significance in PCLO (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.9); Ultra-rare (popmax 0.0813%, sas); Associated with Inborn genetic diseases.

What condition is associated with PCLO p.Gly1663Glu (c.4988G>A)?

PCLO p.Gly1663Glu (c.4988G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PCLO p.Gly1663Glu (c.4988G>A) in the general population?

PCLO p.Gly1663Glu (c.4988G>A) is ultra-rare (popmax 0.0813%, sas) (gnomAD).

What do computational predictors say about PCLO p.Gly1663Glu (c.4988G>A)?

AlphaMissense predicts likely pathogenic (score 0.9) — an in-silico prediction, not a clinical call.

PCLO p.Gly1663Glu

c.4988G>A · rs548515602 · VCV1422443

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0813%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9	likely pathogenic · top 10% in PCLO
REVEL	0.326	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 246 kb · p 0.0018 · regional, not allelic
Overall
CADD	21.7	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 0.0813% South Asian · 74/91,070 alleles

Filtering AF 0.0663% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0608%

Overall 0.00502% 81/1,613,448 alleles · ultra-rare exomes 71/1,461,236 · genomes 10/152,212 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0813%	1,231
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.000339%	294,939

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.Gly1663Glu
Coding: c.4988G>A
MANE Select: NM_033026
dbSNP: rs548515602
Type: single nucleotide variant
Location: chr7:82955965 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Residue 1663: the 'disordered' 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-gly1663glu (accessed [today's date]).

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