Is PIGM p.Ala72Asp (c.215C>A) pathogenic?

PIGM p.Ala72Asp (c.215C>A) is classified Uncertain significance in PIGM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.186); Very rare (popmax 0.00212%, nfe).

How common is PIGM p.Ala72Asp (c.215C>A) in the general population?

PIGM p.Ala72Asp (c.215C>A) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about PIGM p.Ala72Asp (c.215C>A)?

AlphaMissense predicts likely benign (score 0.186) — an in-silico prediction, not a clinical call.

PIGM p.Ala72Asp

c.215C>A · rs768012131 · VCV3212805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.186 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.186	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -4.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.56, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,268 bp · p 0.65 · regional, not allelic
Overall
CADD	21.7	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,180,052 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00161% 26/1,614,090 alleles · very rare exomes 18/1,461,890 · genomes 8/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,202
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Ala72Asp
Coding: c.215C>A
MANE Select: NM_145167
dbSNP: rs768012131
Type: single nucleotide variant
Location: chr1:160031525 (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.Ala72= Likely benign ★ same residue
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

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-ala72asp (accessed [today's date]).

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