Is DLX4 p.Ser68= (c.204C>T) pathogenic?

DLX4 p.Ser68= (c.204C>T) is classified Benign/Likely benign in DLX4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-06). Low-frequency (popmax 1.08%, eas); Associated with orofacial cleft 15.

What condition is associated with DLX4 p.Ser68= (c.204C>T)?

DLX4 p.Ser68= (c.204C>T) is associated with orofacial cleft 15 (ClinVar).

How common is DLX4 p.Ser68= (c.204C>T) in the general population?

DLX4 p.Ser68= (c.204C>T) is low-frequency (popmax 1.08%, eas) (gnomAD).

DLX4 p.Ser68=

c.204C>T · rs200579401 · VCV727636

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, eas)

Conditions

orofacial cleft 15

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 1.5	GERP -0.89, phastCons 1
Overall
CADD	8.977	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.08% East Asian · 485/44,834 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.971%

Overall 0.0378% 608/1,608,234 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.08%	92
Ashkenazi Jewishnot grpmax-eligible	0.159%	630
Admixed American	0.0417%	2,400
Remaining individualsnot grpmax-eligible	0.0368%	2,716
Middle Eastern	0.0165%	6,062
African / African-American	0.004%	25,002
South Asian	0.0022%	45,522
European (non-Finnish)	0.00186%	53,633

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: DLX4
Protein: p.Ser68=
Coding: c.204C>T
MANE Select: NM_138281
dbSNP: rs200579401
Type: single nucleotide variant
Location: chr17:49969672 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.80

Full DLX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

orofacial cleft 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLX4 p.Ala152Val Uncertain significance ★ same condition
DLX4 p.Gln183fs Uncertain significance ★ same condition
DLX4 p.Ala77Thr Uncertain significance ★★ ⚠ same type
DLX4 p.Leu201His Uncertain significance ★★ ⚠ same type
DLX4 p.Ser203Thr Uncertain significance ★★ ⚠ same type
DLX4 p.Ala94= Likely benign ★★ same type
DLX4 p.Arg135Pro Likely benign ★★ same type
DLX4 p.Ala143Val Uncertain significance ★ ⚠ same type

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/dlx4-p-ser68 (accessed [today's date]).

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