Is DHTKD1 p.Ser307Phe (c.920C>T) pathogenic?

DHTKD1 p.Ser307Phe (c.920C>T) is classified Uncertain significance in DHTKD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-24). AlphaMissense: likely benign (0.1255); Very rare (popmax 0.00133%, afr); Associated with Charcot-Marie-Tooth disease axonal type 2Q.

What condition is associated with DHTKD1 p.Ser307Phe (c.920C>T)?

DHTKD1 p.Ser307Phe (c.920C>T) is associated with Charcot-Marie-Tooth disease axonal type 2Q, 2-aminoadipic 2-oxoadipic aciduria (ClinVar).

How common is DHTKD1 p.Ser307Phe (c.920C>T) in the general population?

DHTKD1 p.Ser307Phe (c.920C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DHTKD1 p.Ser307Phe (c.920C>T)?

AlphaMissense predicts likely benign (score 0.1255) — an in-silico prediction, not a clinical call.

DHTKD1 p.Ser307Phe

Q: How is Autosomal dominant Charcot-Marie-Tooth disease type 2Q inherited?

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

c.920C>T · rs777908204 · VCV1033500

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1255 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease axonal type 2Q

Computational evidence

Protein change
AlphaMissense	0.1255	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -5.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 52 kb · p 0.072 · regional, not allelic
Overall
CADD	21.4	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 0.00133% African / African-American · 1/74,922 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000929% 15/1,614,046 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,922
European (non-Finnish)	0.00119%	84,289

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: DHTKD1
Protein: p.Ser307Phe
Coding: c.920C>T
MANE Select: NM_018706
dbSNP: rs777908204
Type: single nucleotide variant
Location: chr10:12089188 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 307: the 'disordered' region; an α-helix

Full DHTKD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease axonal type 2Q — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 2-aminoadipic 2-oxoadipic aciduria

For Autosomal dominant Charcot-Marie-Tooth disease type 2Q (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

DHTKD1 c.1671+1G>A Likely pathogenic ★★ same condition
DHTKD1 c.1897-1G>A Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 c.2320-2A>T Likely pathogenic ★★ same condition
DHTKD1 c.2572+1G>A Likely pathogenic ★★ same condition
DHTKD1 p.Arg163Ter Pathogenic ★★ same condition
DHTKD1 p.Arg410Ter Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 p.Arg455Ter Pathogenic/Likely pathogenic ★★ same condition
DHTKD1 p.Arg712Ter Pathogenic/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/dhtkd1-p-ser307phe (accessed [today's date]).

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