Is SETD1A p.Ala702Pro (c.2104G>C) pathogenic?

SETD1A p.Ala702Pro (c.2104G>C) is classified Likely benign in SETD1A (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-24). AlphaMissense: likely benign (0.1335); Ultra-rare (popmax 0.0473%, afr); Associated with Inborn genetic diseases.

What condition is associated with SETD1A p.Ala702Pro (c.2104G>C)?

SETD1A p.Ala702Pro (c.2104G>C) is associated with Inborn genetic diseases (ClinVar).

How common is SETD1A p.Ala702Pro (c.2104G>C) in the general population?

SETD1A p.Ala702Pro (c.2104G>C) is ultra-rare (popmax 0.0473%, afr) (gnomAD).

What do computational predictors say about SETD1A p.Ala702Pro (c.2104G>C)?

AlphaMissense predicts likely benign (score 0.1335) — an in-silico prediction, not a clinical call.

SETD1A p.Ala702Pro

c.2104G>C · rs150802841 · VCV3054928

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1335 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0473%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1335	likely benign
REVEL	0.44	indeterminate
SaProt	LLR -5.65	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 2.9	GERP -1.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 981 bp · p 0.032 · regional, not allelic
Overall
CADD	12.91	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

Grpmax group 0.0473% African / African-American · 35/73,950 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0307%

Overall 0.00291% 46/1,580,618 alleles · ultra-rare exomes 24/1,428,730 · genomes 22/151,888 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0473%	2,113
Admixed American	0.0126%	7,941
Remaining individualsnot grpmax-eligible	0.00657%	15,225

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: SETD1A
Protein: p.Ala702Pro
Coding: c.2104G>C
MANE Select: NM_014712
dbSNP: rs150802841
Type: single nucleotide variant
Location: chr16:30965985 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.20 · 4 PDB
Residue 702: 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.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
SETD1A p.Glu1009Lys Uncertain significance ★★ ⚠ same condition
SETD1A p.Glu905Lys 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-ala702pro (accessed [today's date]).

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