Is SETD1B p.Ala338Val (c.1013C>T) pathogenic?

SETD1B p.Ala338Val (c.1013C>T) is classified Likely benign in SETD1B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.0842); Rare (popmax 0.641%, afr).

How common is SETD1B p.Ala338Val (c.1013C>T) in the general population?

SETD1B p.Ala338Val (c.1013C>T) is rare (popmax 0.641%, afr) (gnomAD).

What do computational predictors say about SETD1B p.Ala338Val (c.1013C>T)?

AlphaMissense predicts likely benign (score 0.0842) — an in-silico prediction, not a clinical call.

SETD1B p.Ala338Val

c.1013C>T · rs200105126 · VCV2643421

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0842 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.641%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0842	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -7.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP 0.14
Regional constraint	o/e 0.98	unconstrained · MANE · 795 bp · p 0.65 · regional, not allelic
Overall
CADD	10.83	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 0.641% African / African-American · 469/73,154 alleles

Filtering AF 0.593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.574%

Overall 0.0503% 780/1,551,014 alleles · rare exomes 462/1,398,730 · genomes 318/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.641%	156
Finnishnot grpmax-eligible	0.105%	956
Admixed American	0.0745%	1,342
Remaining individualsnot grpmax-eligible	0.0516%	1,939
Middle Eastern	0.0334%	2,996
European (non-Finnish)	0.0153%	6,517
East Asian	0.00244%	40,918
South Asian	0.00119%	84,062

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: SETD1B
Protein: p.Ala338Val
Coding: c.1013C>T
MANE Select: NM_001353345
dbSNP: rs200105126
Type: single nucleotide variant
Location: chr12:121809958 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 46.43 · 4 PDB

Full SETD1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SETD1B p.Arg1329Ter Pathogenic ★★ same type
SETD1B p.Arg1703Ter Pathogenic/Likely pathogenic ★★ same type
SETD1B p.Arg1748Cys Pathogenic/Likely pathogenic ★★ same type
SETD1B p.Arg1792Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
SETD1B p.Arg1825Trp Likely pathogenic ★★ same type
SETD1B p.Arg1902Cys Pathogenic/Likely pathogenic ★★ same type
SETD1B p.Gln780Ter Pathogenic/Likely pathogenic ★★ same type
SETD1B p.Glu1948Lys 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/setd1b-p-ala338val (accessed [today's date]).

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