Is MCPH1 p.Asp668fs (c.2002del) pathogenic?

MCPH1 p.Asp668fs (c.2002del) is classified Likely pathogenic in MCPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-29). No gnomAD frequency available for this variant; Associated with microcephaly 1, primary, autosomal recessive.

What condition is associated with MCPH1 p.Asp668fs (c.2002del)?

MCPH1 p.Asp668fs (c.2002del) is associated with microcephaly 1, primary, autosomal recessive (ClinVar).

How common is MCPH1 p.Asp668fs (c.2002del) in the general population?

MCPH1 p.Asp668fs (c.2002del) is no gnomAD frequency available for this variant (gnomAD).

MCPH1 p.Asp668fs

c.2002del · rs1809112398 · VCV931382

Likely pathogenic Single submitter

Classification

Likely 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

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 6.1	GERP 1.8, 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: MCPH1
Protein: p.Asp668fs
Coding: c.2002del
MANE Select: NM_024596
dbSNP: rs1809112398
Type: Deletion
Location: chr8:6480741 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 9 PDB
Residue 668: 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.Asp678fs 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-asp668fs (accessed [today's date]).

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