Is DLX4 p.Ala152Val (c.455C>T) pathogenic?

DLX4 p.Ala152Val (c.455C>T) is classified Uncertain significance in DLX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-15). AlphaMissense: likely benign (0.261); Very rare (popmax 0.00178%, nfe); Associated with orofacial cleft 15.

What condition is associated with DLX4 p.Ala152Val (c.455C>T)?

DLX4 p.Ala152Val (c.455C>T) is associated with orofacial cleft 15 (ClinVar).

How common is DLX4 p.Ala152Val (c.455C>T) in the general population?

DLX4 p.Ala152Val (c.455C>T) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about DLX4 p.Ala152Val (c.455C>T)?

AlphaMissense predicts likely benign (score 0.261) — an in-silico prediction, not a clinical call.

DLX4 p.Ala152Val

c.455C>T · VCV4883419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.261 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

orofacial cleft 15

Computational evidence

Protein change
AlphaMissense	0.261	likely benign
REVEL	0.739	pathogenic-leaning
SaProt	LLR -11.89	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	GERP -0.07, phastCons 0.81
Regional constraint	o/e 0.99	unconstrained · MANE · 4,471 bp · p 0.8 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,180,036 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00173% 28/1,613,876 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0096%	10,415
European (non-Finnish)grpmax	0.00178%	56,192
South Asian	0.0011%	91,086

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala152Val
Coding: c.455C>T
MANE Select: NM_138281
Type: single nucleotide variant
Location: chr17:49973244 (GRCh38)
Gene constraint: LOEUF 1.056 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.80
Residue 152: a DNA-binding region

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.Ser68= Benign/Likely benign ★★ 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-ala152val (accessed [today's date]).

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