Is PGM3 p.Ile109Phe (c.325A>T) pathogenic?

PGM3 p.Ile109Phe (c.325A>T) is classified Conflicting classifications of pathogenicity in PGM3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-14). AlphaMissense: likely benign (0.1234); Rare (popmax 0.121%, afr); Associated with Inborn genetic diseases.

What condition is associated with PGM3 p.Ile109Phe (c.325A>T)?

PGM3 p.Ile109Phe (c.325A>T) is associated with Inborn genetic diseases, immunodeficiency 23 (ClinVar).

How common is PGM3 p.Ile109Phe (c.325A>T) in the general population?

PGM3 p.Ile109Phe (c.325A>T) is rare (popmax 0.121%, afr) (gnomAD).

What do computational predictors say about PGM3 p.Ile109Phe (c.325A>T)?

AlphaMissense predicts likely benign (score 0.1234) — an in-silico prediction, not a clinical call.

PGM3 p.Ile109Phe

c.325A>T · rs140499200 · VCV541843

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1234 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1234	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -9.31	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 4.2	GERP 2.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	23.0	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 0.121% African / African-American · 91/75,056 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0936%

Overall 0.0062% 100/1,614,018 alleles · rare exomes 55/1,461,670 · genomes 45/152,348 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.121%	825
Admixed American	0.00833%	12,006
Remaining individualsnot grpmax-eligible	0.0064%	15,625

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: PGM3
Protein: p.Ile109Phe
Coding: c.325A>T
MANE Select: NM_015599
dbSNP: rs140499200
Type: single nucleotide variant
Location: chr6:83188678 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: immunodeficiency 23

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-ile109phe (accessed [today's date]).

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