Is DLX1 p.Pro235Ser (c.703C>T) pathogenic?

DLX1 p.Pro235Ser (c.703C>T) is classified Uncertain significance in DLX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely benign (0.1886); Very rare (popmax 0.00085%, nfe).

How common is DLX1 p.Pro235Ser (c.703C>T) in the general population?

DLX1 p.Pro235Ser (c.703C>T) is very rare (popmax 0.00085%, nfe) (gnomAD).

What do computational predictors say about DLX1 p.Pro235Ser (c.703C>T)?

AlphaMissense predicts likely benign (score 0.1886) — an in-silico prediction, not a clinical call.

DLX1 p.Pro235Ser

c.703C>T · rs1363322593 · VCV2212471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00085%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1886	likely benign
REVEL	0.498	indeterminate
SaProt	LLR -6.54	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 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 184 bp · p 0.8 · regional, not allelic
Overall
CADD	23.9	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 0.00085% European (non-Finnish) · 10/1,176,858 alleles

Filtering AF 0.00043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000622% 10/1,607,744 alleles · very rare

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: DLX1
Protein: p.Pro235Ser
Coding: c.703C>T
MANE Select: NM_178120
dbSNP: rs1363322593
Type: single nucleotide variant
Location: chr2:172088192 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.94 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.67

Full DLX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLX1 p.Ala106Pro Uncertain significance ★ ⚠ same type
DLX1 p.Ala192Val Uncertain significance ★ ⚠ same type
DLX1 p.Ala198Thr Uncertain significance ★ ⚠ same type
DLX1 p.Ala200Thr Uncertain significance ★ ⚠ same type
DLX1 p.Ala200Val Uncertain significance ★ ⚠ same type
DLX1 p.Ala204Val Uncertain significance ★ ⚠ same type
DLX1 p.Arg100Cys Uncertain significance ★ ⚠ same type
DLX1 p.Arg100Leu 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/dlx1-p-pro235ser (accessed [today's date]).

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