Is PIGM p.Pro183Ser (c.547C>T) pathogenic?

PIGM p.Pro183Ser (c.547C>T) is classified Uncertain significance in PIGM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely pathogenic (0.5718); Very rare (popmax 0.00134%, afr).

How common is PIGM p.Pro183Ser (c.547C>T) in the general population?

PIGM p.Pro183Ser (c.547C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about PIGM p.Pro183Ser (c.547C>T)?

AlphaMissense predicts likely pathogenic (score 0.5718) — an in-silico prediction, not a clinical call.

PIGM p.Pro183Ser

c.547C>T · VCV4567863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5718 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5718	likely pathogenic
REVEL	0.773	moderately pathogenic-leaning
SaProt	LLR -14.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,268 bp · p 0.65 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,890 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000743% 12/1,614,008 alleles · very rare exomes 10/1,461,882 · genomes 2/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,890
European (non-Finnish)	0.000932%	107,276

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: PIGM
Protein: p.Pro183Ser
Coding: c.547C>T
MANE Select: NM_145167
Type: single nucleotide variant
Location: chr1:160031193 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.10

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

Similar variants

PIGM p.Met1Thr Likely pathogenic ★★ same type
PIGM p.Arg41Gln Uncertain significance ★★ ⚠ same type
PIGM p.Arg46Lys Uncertain significance ★★ ⚠ same type
PIGM p.Cys317Tyr Uncertain significance ★★ ⚠ same type
PIGM p.Gln334Pro Uncertain significance ★★ ⚠ same type
PIGM p.Glu217Gln Uncertain significance ★★ ⚠ same type
PIGM p.Gly20Asp Uncertain significance ★★ ⚠ same type
PIGM p.His44Tyr 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/pigm-p-pro183ser (accessed [today's date]).

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