Is DLX3 p.Ser52Pro (c.154T>C) pathogenic?

DLX3 p.Ser52Pro (c.154T>C) is classified Uncertain significance in DLX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely benign (0.0827); Ultra-rare (popmax 0.0178%, eas).

How common is DLX3 p.Ser52Pro (c.154T>C) in the general population?

DLX3 p.Ser52Pro (c.154T>C) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about DLX3 p.Ser52Pro (c.154T>C)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

DLX3 p.Ser52Pro

c.154T>C · rs199578857 · VCV1907823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -7.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 1,538 bp · p 0.3 · regional, not allelic
Overall
CADD	19.4	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 0.0178% East Asian · 8/44,882 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000681% 11/1,614,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,610
European (non-Finnish)	0.000254%	393,342

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: DLX3
Protein: p.Ser52Pro
Coding: c.154T>C
MANE Select: NM_005220
dbSNP: rs199578857
Type: single nucleotide variant
Location: chr17:49994845 (GRCh38)
Gene constraint: LOEUF 0.559 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 60.87 · 1 PDB

Full DLX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLX3 p.Gln178His Pathogenic/Likely pathogenic ★★ same type
DLX3 p.Ala214Thr Uncertain significance ★★ ⚠ same type
DLX3 p.Ala45Pro Uncertain significance ★★ ⚠ same type
DLX3 p.Arg146Cys Uncertain significance ★★ ⚠ same type
DLX3 p.Arg228Cys Uncertain significance ★★ ⚠ same type
DLX3 p.Arg7Gly Uncertain significance ★★ same type
DLX3 p.Asn200Ser Uncertain significance ★★ ⚠ same type
DLX3 p.Asn282Lys 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/dlx3-p-ser52pro (accessed [today's date]).

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