Is DHTKD1 p.Pro637= (c.1911A>C) pathogenic?

DHTKD1 p.Pro637= (c.1911A>C) is classified Benign in DHTKD1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with 2-aminoadipic 2-oxoadipic aciduria.

What condition is associated with DHTKD1 p.Pro637= (c.1911A>C)?

DHTKD1 p.Pro637= (c.1911A>C) is associated with 2-aminoadipic 2-oxoadipic aciduria, Charcot-Marie-Tooth disease axonal type 2Q (ClinVar).

How is 2-aminoadipic 2-oxoadipic aciduria inherited?

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

DHTKD1 p.Pro637=

Q: How common is DHTKD1 p.Pro637= (c.1911A>C) in the general population?

DHTKD1 p.Pro637= (c.1911A>C) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1911A>C · rs1701472 · VCV1170353

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

2-aminoadipic 2-oxoadipic aciduria

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 -8.6	GERP -4.1
Overall
CADD	0.397	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,882/44,882 alleles

Filtering AF 99.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 99.8%

Overall 99.2% 1,600,827/1,614,196 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
Amishnot grpmax-eligible	100%	1
Finnishnot grpmax-eligible	100%	1
European (non-Finnish)	100%	1
South Asian	99.9%	1
Ashkenazi Jewishnot grpmax-eligible	99.7%	1
Admixed American	99%	1
Middle Eastern	99%	1
Remaining individualsnot grpmax-eligible	98.8%	1
African / African-American	84.7%	1

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.Pro637=
Coding: c.1911A>C
MANE Select: NM_018706
dbSNP: rs1701472
Type: single nucleotide variant
Location: chr10:12106260 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.19 · 8 PDB
Residue 637: a UniProt-annotated variant site (in aakad)

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

Disease context

2-aminoadipic 2-oxoadipic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease axonal type 2Q

For 2-aminoadipic 2-oxoadipic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

DHTKD1 p.Pro637Arg Uncertain significance ★ same residue
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

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-pro637 (accessed [today's date]).

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