Is PGM3 p.Val210Ala (c.629T>C) pathogenic?

PGM3 p.Val210Ala (c.629T>C) is classified Uncertain significance in PGM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-18). AlphaMissense: ambiguous (0.3834); No allele count reported in gnomAD v4.1 (AN 1,613,252); Associated with immunodeficiency 23.

What condition is associated with PGM3 p.Val210Ala (c.629T>C)?

PGM3 p.Val210Ala (c.629T>C) is associated with immunodeficiency 23 (ClinVar).

How common is PGM3 p.Val210Ala (c.629T>C) in the general population?

PGM3 p.Val210Ala (c.629T>C) is no allele count reported in gnomAD v4.1 (AN 1,613,252) (gnomAD).

How is PGM3-CDG inherited?

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

What do computational predictors say about PGM3 p.Val210Ala (c.629T>C)?

AlphaMissense predicts ambiguous (score 0.3834) — an in-silico prediction, not a clinical call.

PGM3 p.Val210Ala

c.629T>C · rs1395736662 · VCV1518993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3834 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,252)

Conditions

immunodeficiency 23

Computational evidence

Protein change
AlphaMissense	0.3834	ambiguous
REVEL	0.424	indeterminate
SaProt	LLR -10.58	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	22.9	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

No allele count reported in gnomAD v4.1 (AN 1,613,252). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PGM3
Protein: p.Val210Ala
Coding: c.629T>C
MANE Select: NM_015599
dbSNP: rs1395736662
Type: single nucleotide variant
Location: chr6:83181894 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.54

Full PGM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 23 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PGM3-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

PGM3 c.-2-185C>T Pathogenic/Likely pathogenic ★★ same condition
PGM3 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same condition
PGM3 p.Asn246Ser Pathogenic/Likely pathogenic ★★ same condition
PGM3 p.Gln22Ter Pathogenic/Likely pathogenic ★★ same condition
PGM3 p.Gln262Ter Pathogenic/Likely pathogenic ★★ same condition
PGM3 c.389+6G>A Uncertain significance ★★ same condition
PGM3 c.-2-226T>C Uncertain significance ★★ same condition
PGM3 p.Ala402Thr 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/pgm3-p-val210ala (accessed [today's date]).

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