Is SETD1A p.Ser244Phe (c.731C>T) pathogenic?

SETD1A p.Ser244Phe (c.731C>T) is classified Uncertain significance in SETD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). AlphaMissense: likely pathogenic (0.7781); Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with SETD1A p.Ser244Phe (c.731C>T)?

SETD1A p.Ser244Phe (c.731C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SETD1A p.Ser244Phe (c.731C>T) in the general population?

SETD1A p.Ser244Phe (c.731C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about SETD1A p.Ser244Phe (c.731C>T)?

AlphaMissense predicts likely pathogenic (score 0.7781) — an in-silico prediction, not a clinical call.

SETD1A p.Ser244Phe

c.731C>T · VCV3317701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7781 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7781	likely pathogenic
REVEL	0.659	pathogenic-leaning
SaProt	LLR -11.61	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,694 bp · p 0.44 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,876 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000372% 6/1,614,088 alleles · very rare exomes 4/1,461,852 · genomes 2/152,236 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,219
Remaining individualsnot grpmax-eligible	0.0016%	62,504
South Asian	0.0011%	91,074

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.Ser244Phe
Coding: c.731C>T
MANE Select: NM_014712
Type: single nucleotide variant
Location: chr16:30964185 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.20 · 4 PDB
Residue 244: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD1A p.Ser244Pro Uncertain significance ★ ⚠ 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
SETD1A p.Glu1009Lys 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-ser244phe (accessed [today's date]).

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