Is SETD1A p.Ser52fs (c.154_155del) pathogenic?

SETD1A p.Ser52fs (c.154155del) is classified Pathogenic in SETD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). No gnomAD frequency available for this variant; Associated with Inborn genetic diseases.

What condition is associated with SETD1A p.Ser52fs (c.154_155del)?

SETD1A p.Ser52fs (c.154_155del) is associated with Inborn genetic diseases (ClinVar).

How common is SETD1A p.Ser52fs (c.154_155del) in the general population?

SETD1A p.Ser52fs (c.154_155del) is no gnomAD frequency available for this variant (gnomAD).

SETD1A p.Ser52fs

c.154_155del · rs2543833528 · VCV3160576

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SETD1A
Protein: p.Ser52fs
Coding: c.154_155del
MANE Select: NM_014712
dbSNP: rs2543833528
Type: Deletion
Location: chr16:30959093 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.20 · 4 PDB
Residue 52: 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.Pro644fs Pathogenic ★★ same condition
SETD1A p.Arg72fs Pathogenic ★ same condition
SETD1A p.Leu1212fs Pathogenic ★ same condition
SETD1A p.Ser1058fs Pathogenic ★ same condition
SETD1A p.Phe1572fs Uncertain significance ★ same condition
SETD1A p.Ser1231_Arg1236del Uncertain significance ★ same condition
SETD1A p.Ala671Thr Uncertain significance ★★ ⚠ same condition
SETD1A p.Ala840Val 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-ser52fs (accessed [today's date]).

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