How common is DLX5 p.Ser190Phe (c.569C>T) in the general population?

DLX5 p.Ser190Phe (c.569C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLX5 p.Ser190Phe (c.569C>T)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

DLX5 p.Ser190Phe

Q: Is DLX5 p.Ser190Phe (c.569C>T) pathogenic?

DLX5 p.Ser190Phe (c.569C>T) is classified Uncertain significance in DLX5 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with split hand-foot malformation 1 with sensorineural hearing loss.

Q: What condition is associated with DLX5 p.Ser190Phe (c.569C>T)?

DLX5 p.Ser190Phe (c.569C>T) is associated with split hand-foot malformation 1 with sensorineural hearing loss, split hand-foot malformation 1 (ClinVar).

c.569C>T · VCV3382755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

split hand-foot malformation 1 with sensorineural hearing loss

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 7% in DLX5
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -14.06	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 1,213 bp · p 0.00014 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DLX5
Protein: p.Ser190Phe
Coding: c.569C>T
MANE Select: NM_005221
Type: single nucleotide variant
Location: chr7:97021037 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 61.56 · 2 PDB
Residue 190: a DNA-binding region; an α-helix

Full DLX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

split hand-foot malformation 1 with sensorineural hearing loss — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: split hand-foot malformation 1

Similar variants

DLX5 p.Ser229Pro Uncertain significance ★★ ⚠ same condition
DLX5 p.Ala171Val Likely pathogenic ★ same condition
DLX5 p.Leu170Pro Likely pathogenic ★ same condition
DLX5 p.Tyr161His Likely pathogenic ★ same condition
DLX5 p.Ter290Glu Uncertain significance ★ same condition
DLX5 p.Gln178Pro Pathogenic same condition
DLX5 p.Glu39Ter Pathogenic same condition
DLX5 p.Pro280fs 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/dlx5-p-ser190phe (accessed [today's date]).

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