Is PMM2 p.Phe207Ser (c.620T>C) pathogenic?

PMM2 p.Phe207Ser (c.620T>C) is classified Pathogenic/Likely pathogenic in PMM2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-27). AlphaMissense: likely pathogenic (0.9774); Very rare (popmax 0.00833%, amr); Associated with PMM2-congenital disorder of glycosylation.

What condition is associated with PMM2 p.Phe207Ser (c.620T>C)?

PMM2 p.Phe207Ser (c.620T>C) is associated with PMM2-congenital disorder of glycosylation (ClinVar).

How common is PMM2 p.Phe207Ser (c.620T>C) in the general population?

PMM2 p.Phe207Ser (c.620T>C) is very rare (popmax 0.00833%, amr) (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.Phe207Ser (c.620T>C)?

AlphaMissense predicts likely pathogenic (score 0.9774) — an in-silico prediction, not a clinical call.

PMM2 p.Phe207Ser

c.620T>C · rs532870929 · VCV189141

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9774 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PMM2-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.9774	likely pathogenic ✓ concordant with ClinVar
REVEL	0.982	strongly pathogenic-leaning
SaProt	LLR -14.45	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 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 50 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	31.0	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 0.00833% Admixed American · 5/60,014 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.002% 32/1,603,480 alleles · very rare exomes 29/1,451,116 · genomes 3/152,364 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,003
Remaining individualsnot grpmax-eligible	0.00322%	31,092
European (non-Finnish)	0.00214%	46,808

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.Phe207Ser
Coding: c.620T>C
MANE Select: NM_000303
dbSNP: rs532870929
Type: single nucleotide variant
Location: chr16:8813087 (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 207: a β-strand

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.Phe207= 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
PMM2 c.255+2T>C Pathogenic/Likely pathogenic ★★ same condition
PMM2 c.256-1G>C 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-phe207ser (accessed [today's date]).

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