Is SETD1A p.Pro1410= (c.4230A>C) pathogenic?

SETD1A p.Pro1410= (c.4230A>C) is classified Likely benign in SETD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). Rare (popmax 0.363%, afr).

How common is SETD1A p.Pro1410= (c.4230A>C) in the general population?

SETD1A p.Pro1410= (c.4230A>C) is rare (popmax 0.363%, afr) (gnomAD).

SETD1A p.Pro1410=

c.4230A>C · VCV4929517

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.363%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.7	GERP -3.7
Overall
CADD	0.041	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.363% African / African-American · 64/17,610 alleles

Filtering AF 0.292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.266%

Overall 0.182% 591/324,262 alleles · rare exomes 379/280,802 · genomes 212/43,460 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.668%	150
Amishnot grpmax-eligible	0.472%	212
African / African-Americangrpmax	0.363%	275
South Asian	0.26%	385
Remaining individualsnot grpmax-eligible	0.136%	735
European (non-Finnish)	0.124%	807
Middle Eastern	0.105%	950
Admixed American	0.103%	973
Ashkenazi Jewishnot grpmax-eligible	0.0844%	1,185
East Asian	0.0421%	2,373

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1410=
Coding: c.4230A>C
MANE Select: NM_014712
Type: single nucleotide variant
Location: chr16:30980016 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.20 · 4 PDB
Residue 1410: the 'disordered' region; a UniProt-annotated variant site (in nedsid)

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

Similar variants

SETD1A p.Pro1410Ser Uncertain significance ★★ ⚠ same residue
SETD1A p.Pro1410Leu Uncertain significance ★ ⚠ same residue
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
SETD1A p.Arg913Cys Likely pathogenic ★★ ⚠ same type
SETD1A p.Arg990Ter Pathogenic/Likely 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-pro1410 (accessed [today's date]).

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