Is DHODH p.Phe24= (c.72C>T) pathogenic?

DHODH p.Phe24= (c.72C>T) is classified Benign/Likely benign in DHODH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-07). Rare (popmax 0.516%, afr); Associated with postaxial acrofacial dysostosis.

What condition is associated with DHODH p.Phe24= (c.72C>T)?

DHODH p.Phe24= (c.72C>T) is associated with postaxial acrofacial dysostosis (ClinVar).

How common is DHODH p.Phe24= (c.72C>T) in the general population?

DHODH p.Phe24= (c.72C>T) is rare (popmax 0.516%, afr) (gnomAD).

DHODH p.Phe24=

c.72C>T · rs61753576 · VCV320419

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.516%, afr)

Conditions

postaxial acrofacial dysostosis

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 -5.2	GERP -3.1
Overall
CADD	3.538	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.516% African / African-American · 387/75,042 alleles

Filtering AF 0.473% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.457%

Overall 0.0388% 626/1,614,170 alleles · rare exomes 400/1,461,888 · genomes 226/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.516%	194
Admixed American	0.102%	984
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.0864%	1,158
European (non-Finnish)	0.00941%	10,631
East Asian	0.00891%	11,220
South Asian	0.0022%	45,540
Finnishnot grpmax-eligible	0.00156%	64,026

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: DHODH
Protein: p.Phe24=
Coding: c.72C>T
MANE Select: NM_001361
dbSNP: rs61753576
Type: single nucleotide variant
Location: chr16:72012100 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.13 · 106 PDB

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

Disease context

postaxial acrofacial dysostosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DHODH p.Phe24Leu Uncertain significance ★ ⚠ same residue
DHODH p.Arg135Cys Pathogenic/Likely pathogenic ★★ same condition
DHODH p.Arg346Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
DHODH c.*341C>T Uncertain significance ★★ same condition
DHODH p.Arg297His Uncertain significance ★★ ⚠ same condition
DHODH p.Arg35His Uncertain significance ★★ ⚠ same condition
DHODH p.Arg88Ter Uncertain significance ★★ same condition
DHODH p.Asp206Asn 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/dhodh-p-phe24 (accessed [today's date]).

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