Is PMM2 p.Arg162Pro (c.485G>C) pathogenic?

PMM2 p.Arg162Pro (c.485G>C) is classified Likely pathogenic in PMM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). AlphaMissense: likely pathogenic (0.9256); Very rare (popmax 0.000254%, nfe); Associated with PMM2-congenital disorder of glycosylation.

What condition is associated with PMM2 p.Arg162Pro (c.485G>C)?

PMM2 p.Arg162Pro (c.485G>C) is associated with PMM2-congenital disorder of glycosylation (ClinVar).

How common is PMM2 p.Arg162Pro (c.485G>C) in the general population?

PMM2 p.Arg162Pro (c.485G>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is PMM2-CDG inherited?

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

What do computational predictors say about PMM2 p.Arg162Pro (c.485G>C)?

AlphaMissense predicts likely pathogenic (score 0.9256) — an in-silico prediction, not a clinical call.

PMM2 p.Arg162Pro

c.485G>C · rs749716985 · VCV2028388

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9256 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PMM2-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.9256	likely pathogenic ✓ concordant with ClinVar
REVEL	0.747	pathogenic-leaning
SaProt	LLR -18.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.093	GERP -4.4, phastCons 0.42
Regional constraint	o/e 1.26	unconstrained · MANE · 50 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	22.5	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 0.000254% European (non-Finnish) · 3/1,179,304 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,334 alleles · very rare exomes 3/1,461,060 · genomes 0/152,274 · 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: PMM2
Protein: p.Arg162Pro
Coding: c.485G>C
MANE Select: NM_000303
dbSNP: rs749716985
Type: single nucleotide variant
Location: chr16:8811675 (GRCh38)
Gene constraint: LOEUF 1.937 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.66 · 7 PDB
Residue 162: an α-helix; a UniProt-annotated variant site (in cdg1a)

Full PMM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PMM2-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PMM2-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Italy)

Similar variants

PMM2 p.Arg162Trp Pathogenic/Likely pathogenic ★★ ⚠ same residue
PMM2 p.Arg162Gln Uncertain significance ★ ⚠ same residue
PMM2 p.Arg162= Likely benign ★ same residue
PMM2 c.178+1G>A Likely pathogenic ★★ same condition
PMM2 c.178+2T>G Likely pathogenic ★★ same condition
PMM2 c.179-1G>C Pathogenic/Likely pathogenic ★★ same condition
PMM2 c.179-25A>G Likely pathogenic ★★ same condition
PMM2 c.255+1G>A 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/pmm2-p-arg162pro (accessed [today's date]).

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