Is PIGO p.Pro127Ser (c.379C>T) pathogenic?

PIGO p.Pro127Ser (c.379C>T) is classified Uncertain significance in PIGO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-18). AlphaMissense: likely benign (0.2447); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with PIGO p.Pro127Ser (c.379C>T)?

PIGO p.Pro127Ser (c.379C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PIGO p.Pro127Ser (c.379C>T) in the general population?

PIGO p.Pro127Ser (c.379C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PIGO p.Pro127Ser (c.379C>T)?

AlphaMissense predicts likely benign (score 0.2447) — an in-silico prediction, not a clinical call.

PIGO p.Pro127Ser

c.379C>T · VCV3888810

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2447 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2447	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -11.05	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 6,470 bp · p 2e-05 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Overall 0.000137% 2/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,080
European (non-Finnish)	8.47e-05%	1,180,030

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: PIGO
Protein: p.Pro127Ser
Coding: c.379C>T
MANE Select: NM_032634
Type: single nucleotide variant
Location: chr9:35095187 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.57

Full PIGO 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

PIGO p.Pro127Arg Uncertain significance ★ ⚠ same residue
PIGO p.Ala1001Val Uncertain significance ★★ ⚠ same condition
PIGO p.Ala19Ser Uncertain significance ★★ ⚠ same condition
PIGO p.Ala384Val Uncertain significance ★★ ⚠ same condition
PIGO p.Ala419Thr Uncertain significance ★★ ⚠ same condition
PIGO p.Ala452Val Uncertain significance ★★ ⚠ same condition
PIGO p.Ala517Thr Uncertain significance ★★ ⚠ same condition
PIGO p.Ala540Pro 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/pigo-p-pro127ser (accessed [today's date]).

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