Is SETD1A p.Ile875Ser (c.2624T>G) pathogenic?

SETD1A p.Ile875Ser (c.2624T>G) is classified Uncertain significance in SETD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: ambiguous (0.3664); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SETD1A p.Ile875Ser (c.2624T>G)?

SETD1A p.Ile875Ser (c.2624T>G) is associated with Inborn genetic diseases (ClinVar).

How common is SETD1A p.Ile875Ser (c.2624T>G) in the general population?

SETD1A p.Ile875Ser (c.2624T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SETD1A p.Ile875Ser (c.2624T>G)?

AlphaMissense predicts ambiguous (score 0.3664) — an in-silico prediction, not a clinical call.

SETD1A p.Ile875Ser

c.2624T>G · VCV3440157

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3664 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3664	ambiguous
REVEL	0.503	indeterminate
SaProt	LLR -3.96	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 14 kb · p 0.57 · regional, not allelic
Overall
CADD	21.2	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.Ile875Ser
Coding: c.2624T>G
MANE Select: NM_014712
Type: single nucleotide variant
Location: chr16:30967002 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.20 · 4 PDB
Residue 875: a UniProt-annotated variant site (in nedsid)

Full SETD1A 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

SETD1A p.Ile875Val Conflicting classifications of pathogenicity ★ ⚠ same residue
SETD1A p.Ile875= Likely benign same residue
SETD1A p.Ala671Thr Uncertain significance ★★ ⚠ same condition
SETD1A p.Ala840Val Uncertain significance ★★ ⚠ same condition
SETD1A p.Arg1576Trp Uncertain significance ★★ ⚠ same condition
SETD1A p.Arg276Trp Uncertain significance ★★ ⚠ same condition
SETD1A p.Arg385His Uncertain significance ★★ ⚠ same condition
SETD1A p.Cys1638Phe 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/setd1a-p-ile875ser (accessed [today's date]).

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