Is PGM1 p.Val87= (c.261T>C) pathogenic?

PGM1 p.Val87= (c.261T>C) is classified Likely benign in PGM1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-17). Ultra-rare (popmax 0.0267%, afr); Associated with PGM1-congenital disorder of glycosylation.

What condition is associated with PGM1 p.Val87= (c.261T>C)?

PGM1 p.Val87= (c.261T>C) is associated with PGM1-congenital disorder of glycosylation (ClinVar).

How common is PGM1 p.Val87= (c.261T>C) in the general population?

PGM1 p.Val87= (c.261T>C) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

How is PGM1-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PGM1 p.Val87=

c.261T>C · rs147540336 · VCV2044266

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Conditions

PGM1-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.26	GERP -4.2, phastCons 0.39
Overall
CADD	5.244	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% African / African-American · 20/74,886 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00205% 33/1,613,518 alleles · ultra-rare exomes 20/1,461,348 · genomes 13/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,744
Admixed American	0.0167%	5,998
Middle Eastern	0.0165%	6,074
Remaining individualsnot grpmax-eligible	0.0032%	31,230

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: PGM1
Protein: p.Val87=
Coding: c.261T>C
MANE Select: NM_002633
dbSNP: rs147540336
Type: single nucleotide variant
Location: chr1:63629439 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.27 · 16 PDB
Residue 87: a β-strand

Full PGM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PGM1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PGM1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PGM1 p.Val87Ile Uncertain significance ★ ⚠ same residue
PGM1 p.Arg217Ter Pathogenic ★★ same condition
PGM1 p.Arg293Ter Pathogenic/Likely pathogenic ★★ same condition
PGM1 p.Arg499Ter Pathogenic/Likely pathogenic ★★ same condition
PGM1 p.Arg503Ter Pathogenic ★★ same condition
PGM1 p.Arg515Gln Pathogenic/Likely pathogenic ★★ same condition
PGM1 p.Asp263Tyr Pathogenic/Likely pathogenic ★★ same condition
PGM1 p.Gly291Arg Pathogenic/Likely pathogenic ★★ 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/pgm1-p-val87 (accessed [today's date]).

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