Is DLX5 p.Ser83Phe (c.248C>T) pathogenic?

DLX5 p.Ser83Phe (c.248C>T) is classified Uncertain significance in DLX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.2124); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DLX5 p.Ser83Phe (c.248C>T)?

DLX5 p.Ser83Phe (c.248C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DLX5 p.Ser83Phe (c.248C>T) in the general population?

DLX5 p.Ser83Phe (c.248C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DLX5 p.Ser83Phe (c.248C>T)?

AlphaMissense predicts likely benign (score 0.2124) — an in-silico prediction, not a clinical call.

DLX5 p.Ser83Phe

c.248C>T · VCV4241265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2124	likely benign
REVEL	0.47	indeterminate
SaProt	LLR -8.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,376 bp · p 0.21 · regional, not allelic
Overall
CADD	29.1	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 0.00167% Admixed American · 1/60,016 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,614,130 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,016
European (non-Finnish)	0.000424%	236,011

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: DLX5
Protein: p.Ser83Phe
Coding: c.248C>T
MANE Select: NM_005221
Type: single nucleotide variant
Location: chr7:97024376 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 61.56 · 2 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLX5 p.Asp44Tyr Uncertain significance ★★ ⚠ same condition
DLX5 p.His238Asn Uncertain significance ★★ ⚠ same condition
DLX5 p.Pro30Leu Uncertain significance ★★ ⚠ same condition
DLX5 p.Tyr108Cys Uncertain significance ★★ ⚠ same condition
DLX5 p.Ala89Asp Uncertain significance ★ ⚠ same condition
DLX5 p.Arg8Thr Uncertain significance ★ ⚠ same condition
DLX5 p.Asp16His Uncertain significance ★ ⚠ same condition
DLX5 p.Asp211Asn 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-ser83phe (accessed [today's date]).

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