Is PGAM5 p.Ser113Phe (c.338C>T) pathogenic?

PGAM5 p.Ser113Phe (c.338C>T) is classified Uncertain significance in PGAM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: likely benign (0.1273); Very rare (popmax 0.000254%, nfe).

How common is PGAM5 p.Ser113Phe (c.338C>T) in the general population?

PGAM5 p.Ser113Phe (c.338C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about PGAM5 p.Ser113Phe (c.338C>T)?

AlphaMissense predicts likely benign (score 0.1273) — an in-silico prediction, not a clinical call.

PGAM5 p.Ser113Phe

c.338C>T · rs2542267542 · VCV2609501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1273 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1273	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -6.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 9,948 bp · p 0.22 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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) · 3/1,179,896 alleles

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

Overall 0.000186% 3/1,613,110 alleles · very rare exomes 3/1,460,770 · genomes 0/152,340 · 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: PGAM5
Protein: p.Ser113Phe
Coding: c.338C>T
MANE Select: NM_001170543
dbSNP: rs2542267542
Type: single nucleotide variant
Location: chr12:132715004 (GRCh38)
Gene constraint: LOEUF 1.395 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.94 · 10 PDB

Full PGAM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGAM5 c.191+177G>A Benign ★★ same type
PGAM5 c.191+68A>G Benign ★★ same type
PGAM5 c.497-65G>T Benign ★★ same type
PGAM5 c.719+22C>T Benign ★★ same type
PGAM5 c.719+63A>G Benign ★★ same type
PGAM5 c.719+647C>T Benign ★★ same type
PGAM5 c.719+676C>G Benign ★★ same type
PGAM5 c.719+795T>C Benign ★★ same type

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/pgam5-p-ser113phe (accessed [today's date]).

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