Is PIGV p.Pro44Ser (c.130C>T) pathogenic?

PIGV p.Pro44Ser (c.130C>T) is classified Uncertain significance in PIGV (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-29). AlphaMissense: likely benign (0.1631); Very rare (popmax 0.000169%, nfe).

How common is PIGV p.Pro44Ser (c.130C>T) in the general population?

PIGV p.Pro44Ser (c.130C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about PIGV p.Pro44Ser (c.130C>T)?

AlphaMissense predicts likely benign (score 0.1631) — an in-silico prediction, not a clinical call.

PIGV p.Pro44Ser

c.130C>T · rs2124193175 · VCV1357148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1631 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1631	likely benign
REVEL	0.776	moderately pathogenic-leaning
SaProt	LLR -9.41	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 7,025 bp · p 0.0089 · regional, not allelic
Overall
CADD	25.6	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 0.000169% European (non-Finnish) · 2/1,180,038 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,250 alleles · very rare exomes 2/1,461,892 · genomes 0/152,358 · 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: PIGV
Protein: p.Pro44Ser
Coding: c.130C>T
MANE Select: NM_017837
dbSNP: rs2124193175
Type: single nucleotide variant
Location: chr1:26794164 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.22

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

Similar variants

PIGV p.Pro44Ala Uncertain significance ★ ⚠ same residue
PIGV p.Ala341Glu Pathogenic/Likely pathogenic ★★ same type
PIGV p.Ala418Asp Likely pathogenic ★★ same type
PIGV p.Arg19Cys Likely pathogenic ★★ ⚠ same type
PIGV p.Arg203Cys Pathogenic/Likely pathogenic ★★ same type
PIGV p.Cys156Tyr Pathogenic/Likely pathogenic ★★ same type
PIGV p.Ala386Thr Uncertain significance ★★ ⚠ same type
PIGV p.Ala440Thr 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/pigv-p-pro44ser (accessed [today's date]).

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