Is SETD1A p.Thr236Pro (c.706A>C) pathogenic?

SETD1A p.Thr236Pro (c.706A>C) is classified Likely benign in SETD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-04). AlphaMissense: likely benign (0.1059); Absent from gnomAD v4.1; Associated with Developmental disorder.

What condition is associated with SETD1A p.Thr236Pro (c.706A>C)?

SETD1A p.Thr236Pro (c.706A>C) is associated with Developmental disorder (ClinVar).

How common is SETD1A p.Thr236Pro (c.706A>C) in the general population?

SETD1A p.Thr236Pro (c.706A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SETD1A p.Thr236Pro (c.706A>C)?

AlphaMissense predicts likely benign (score 0.1059) — an in-silico prediction, not a clinical call.

SETD1A p.Thr236Pro

c.706A>C · rs2143483723 · VCV1343187

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1059 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Developmental disorder

Computational evidence

Protein change
AlphaMissense	0.1059	likely benign
REVEL	0.395	indeterminate
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,694 bp · p 0.44 · regional, not allelic
Overall
CADD	26.3	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

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: SETD1A
Protein: p.Thr236Pro
Coding: c.706A>C
MANE Select: NM_014712
dbSNP: rs2143483723
Type: single nucleotide variant
Location: chr16:30964160 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.20 · 4 PDB
Residue 236: a UniProt-annotated variant site (in nedsid); the 'disordered' region

Full SETD1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Developmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD1A p.Thr236Ile Uncertain significance ★ ⚠ same residue
SETD1A p.Arg948Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
SETD1A p.Gln1604Pro Uncertain significance ★ ⚠ same condition
SETD1A p.Ser252Gly Likely benign ★ same condition
SETD1A c.518-2A>G Pathogenic ★★ same type
SETD1A p.Arg1571Ter Pathogenic/Likely pathogenic ★★ same type
SETD1A p.Arg176Ter Pathogenic/Likely pathogenic ★★ same type
SETD1A p.Arg668Ter Pathogenic ★★ 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/setd1a-p-thr236pro (accessed [today's date]).

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