Is MMADHC p.Asp69= (c.207T>C) pathogenic?

MMADHC p.Asp69= (c.207T>C) is classified Likely benign in MMADHC (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-21). Very rare (popmax 0.0011%, sas); Associated with methylmalonic aciduria and homocystinuria type cblD.

What condition is associated with MMADHC p.Asp69= (c.207T>C)?

MMADHC p.Asp69= (c.207T>C) is associated with methylmalonic aciduria and homocystinuria type cblD (ClinVar).

How common is MMADHC p.Asp69= (c.207T>C) in the general population?

MMADHC p.Asp69= (c.207T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Methylmalonic acidemia with homocystinuria inherited?

Typically Autosomal recessive, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MMADHC p.Asp69=

c.207T>C · rs1327529103 · VCV1090920

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

methylmalonic aciduria and homocystinuria type cblD

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 5.5	GERP -0.64, phastCons 1
Overall
CADD	9.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 6.2e-05% 1/1,614,052 alleles · very rare exomes 1/1,461,726 · genomes 0/152,326 · 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: MMADHC
Protein: p.Asp69=
Coding: c.207T>C
MANE Select: NM_015702
dbSNP: rs1327529103
Type: single nucleotide variant
Location: chr2:149579596 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.67 · 4 PDB
Residue 69: a UniProt-annotated variant site (in macd)

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

Disease context

methylmalonic aciduria and homocystinuria type cblD — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Methylmalonic acidemia with homocystinuria (Orphanet):

Inheritance: Autosomal recessive, X-linked recessive
Onset: All ages

Similar variants

MMADHC c.10-1G>A Pathogenic/Likely pathogenic ★★ same condition
MMADHC c.10-1G>C Likely pathogenic ★★ same condition
MMADHC c.154+1G>A Pathogenic/Likely pathogenic ★★ same condition
MMADHC c.610-1G>A Likely pathogenic ★★ same condition
MMADHC p.Arg158Ter Pathogenic ★★ same condition
MMADHC p.Arg216Ter Pathogenic/Likely pathogenic ★★ same condition
MMADHC p.Arg250Ter Pathogenic/Likely pathogenic ★★ same condition
MMADHC p.Gln180Ter 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/mmadhc-p-asp69 (accessed [today's date]).

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