Is MGST3 p.Pro70Ser (c.208C>T) pathogenic?

MGST3 p.Pro70Ser (c.208C>T) is classified Uncertain significance in MGST3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-05). AlphaMissense: likely benign (0.1093); Very rare (popmax 0.00267%, afr).

How common is MGST3 p.Pro70Ser (c.208C>T) in the general population?

MGST3 p.Pro70Ser (c.208C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about MGST3 p.Pro70Ser (c.208C>T)?

AlphaMissense predicts likely benign (score 0.1093) — an in-silico prediction, not a clinical call.

MGST3 p.Pro70Ser

c.208C>T · VCV4054563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1093	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -3.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP -0.29, phastCons 0.97
Regional constraint	o/e 0.81	unconstrained · MANE · 5,653 bp · p 0.0069 · regional, not allelic
Overall
CADD	17.9	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 0.00267% African / African-American · 2/74,818 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00093% 15/1,613,258 alleles · very rare exomes 14/1,461,354 · genomes 1/151,904 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,409
East Asian	0.00223%	44,840
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	0.000933%	107,237

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: MGST3
Protein: p.Pro70Ser
Coding: c.208C>T
MANE Select: NM_004528
Type: single nucleotide variant
Location: chr1:165651994 (GRCh38)
Gene constraint: LOEUF 1.24 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.78

Full MGST3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MGST3 p.Ala92Pro Uncertain significance ★ ⚠ same type
MGST3 p.Arg84Cys Uncertain significance ★ ⚠ same type
MGST3 p.Arg84His Uncertain significance ★ ⚠ same type
MGST3 p.Arg97Gln Uncertain significance ★ ⚠ same type
MGST3 p.Asn28Ser Uncertain significance ★ ⚠ same type
MGST3 p.Gly138Asp Uncertain significance ★ ⚠ same type
MGST3 p.Gly96Ala Uncertain significance ★ ⚠ same type
MGST3 p.His82Tyr Uncertain significance ★ ⚠ 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/mgst3-p-pro70ser (accessed [today's date]).

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