Is MDH2 p.Ser20= (c.60G>A) pathogenic?

MDH2 p.Ser20= (c.60G>A) is classified Likely benign in MDH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-04). Very rare (popmax 0.00274%, afr); Associated with Inborn genetic diseases.

What condition is associated with MDH2 p.Ser20= (c.60G>A)?

MDH2 p.Ser20= (c.60G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MDH2 p.Ser20= (c.60G>A) in the general population?

MDH2 p.Ser20= (c.60G>A) is very rare (popmax 0.00274%, afr) (gnomAD).

MDH2 p.Ser20=

c.60G>A · rs1132848 · VCV1751603

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00274%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	phastCons 0.009
Overall
CADD	10.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00274% African / African-American · 2/72,948 alleles

Filtering AF 0.000455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00017%

Overall 0.000652% 10/1,534,676 alleles · very rare exomes 9/1,382,466 · genomes 1/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00274%	36,474
East Asian	0.00244%	40,906
European (non-Finnish)	0.000611%	163,749

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: MDH2
Protein: p.Ser20=
Coding: c.60G>A
MANE Select: NM_005918
dbSNP: rs1132848
Type: single nucleotide variant
Location: chr7:76048220 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.49 · 7 PDB

Full MDH2 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

Similar variants

MDH2 p.Ser20Leu Uncertain significance ★ ⚠ same residue
MDH2 p.Ala135Gly Uncertain significance ★★ ⚠ same condition
MDH2 p.Ala141Thr Uncertain significance ★★ same condition
MDH2 p.Ala177Thr Uncertain significance ★★ ⚠ same condition
MDH2 p.Ala21Val Uncertain significance ★★ ⚠ same condition
MDH2 p.Ala242Val Uncertain significance ★★ ⚠ same condition
MDH2 p.Ala256Thr Uncertain significance ★★ ⚠ same condition
MDH2 p.Ala325Val 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/mdh2-p-ser20 (accessed [today's date]).

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