Is MCPH1 p.Val697fs (c.2089del) pathogenic?

MCPH1 p.Val697fs (c.2089del) is classified Likely pathogenic in MCPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). Associated with microcephaly 1, primary, autosomal recessive.

What condition is associated with MCPH1 p.Val697fs (c.2089del)?

MCPH1 p.Val697fs (c.2089del) is associated with microcephaly 1, primary, autosomal recessive (ClinVar).

MCPH1 p.Val697fs

c.2089del · VCV3595811

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

microcephaly 1, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.8	GERP -3.6

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

Variant & gene context

Gene: MCPH1
Protein: p.Val697fs
Coding: c.2089del
MANE Select: NM_024596
Type: Deletion
Location: chr8:6480829 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 9 PDB
Residue 697: the brct 2 domain; an α-helix

Full MCPH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly 1, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MCPH1 p.Lys107fs Pathogenic/Likely pathogenic ★★ same condition
MCPH1 p.Lys26fs Pathogenic/Likely pathogenic ★★ same condition
MCPH1 p.Ser191fs Pathogenic/Likely pathogenic ★★ same condition
MCPH1 p.Ser623_Cys624insTer Pathogenic/Likely pathogenic ★★ same condition
MCPH1 c.1935+1_1935+5del Likely pathogenic ★ same condition
MCPH1 c.22+2_22+4del Pathogenic ★ same condition
MCPH1 p.Arg469fs Likely pathogenic ★ same condition
MCPH1 p.Asp668fs Likely pathogenic ★ 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/mcph1-p-val697fs (accessed [today's date]).

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