Is ACSF3 p.Asp235= (c.705C>T) pathogenic?

ACSF3 p.Asp235= (c.705C>T) is classified Likely benign in ACSF3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.078%, eas); Associated with combined malonic and methylmalonic acidemia.

What condition is associated with ACSF3 p.Asp235= (c.705C>T)?

ACSF3 p.Asp235= (c.705C>T) is associated with combined malonic and methylmalonic acidemia (ClinVar).

How common is ACSF3 p.Asp235= (c.705C>T) in the general population?

ACSF3 p.Asp235= (c.705C>T) is ultra-rare (popmax 0.078%, eas) (gnomAD).

How is Combined malonic and methylmalonic acidemia inherited?

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

ACSF3 p.Asp235=

c.705C>T · rs766852572 · VCV744677

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, eas)

Conditions

combined malonic and methylmalonic acidemia

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 -9.8	GERP -3.1
Overall
CADD	8.315	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.078% East Asian · 35/44,878 alleles

Filtering AF 0.0576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0506%

Overall 0.0049% 79/1,613,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.078%	1,282
Middle Eastern	0.033%	3,027
Admixed American	0.00666%	15,004
South Asian	0.00549%	18,217
Remaining individualsnot grpmax-eligible	0.0032%	31,250
European (non-Finnish)	0.00263%	38,065

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: ACSF3
Protein: p.Asp235=
Coding: c.705C>T
MANE Select: NM_001243279
dbSNP: rs766852572
Type: single nucleotide variant
Location: chr16:89102642 (GRCh38)
Gene constraint: LOEUF 1.715 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.58

Full ACSF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined malonic and methylmalonic acidemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined malonic and methylmalonic acidemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (United States)

Similar variants

ACSF3 c.1366+1G>A Likely pathogenic ★★ same condition
ACSF3 c.1501+1G>A Likely pathogenic ★★ same condition
ACSF3 c.1501+1G>T Likely pathogenic ★★ same condition
ACSF3 c.1502-2A>G Pathogenic/Likely pathogenic ★★ same condition
ACSF3 c.1613+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACSF3 c.666+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACSF3 c.666+1G>T Likely pathogenic ★★ same condition
ACSF3 c.667-2A>G Likely 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/acsf3-p-asp235 (accessed [today's date]).

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