Is MCPH1 p.Cys371= (c.1113C>T) pathogenic?

MCPH1 p.Cys371= (c.1113C>T) is classified Conflicting classifications of pathogenicity in MCPH1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-04). Ultra-rare (popmax 0.0318%, sas); Associated with microcephaly 1, primary, autosomal recessive.

What condition is associated with MCPH1 p.Cys371= (c.1113C>T)?

MCPH1 p.Cys371= (c.1113C>T) is associated with microcephaly 1, primary, autosomal recessive (ClinVar).

How common is MCPH1 p.Cys371= (c.1113C>T) in the general population?

MCPH1 p.Cys371= (c.1113C>T) is ultra-rare (popmax 0.0318%, sas) (gnomAD).

MCPH1 p.Cys371=

c.1113C>T · rs587783732 · VCV158816

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0318%, sas)

Conditions

microcephaly 1, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.1
Overall
CADD	0.361	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0318% South Asian · 29/91,080 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.0018% 29/1,614,116 alleles · ultra-rare exomes 29/1,461,868 · genomes 0/152,248 · joint denominator

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: MCPH1
Protein: p.Cys371=
Coding: c.1113C>T
MANE Select: NM_024596
dbSNP: rs587783732
Type: single nucleotide variant
Location: chr8:6444835 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 9 PDB
Residue 371: the 'disordered' region

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.Cys371Tyr Uncertain significance ★ ⚠ same residue
MCPH1 c.321+2T>C Likely pathogenic ★★ same condition
MCPH1 c.322-1G>C Pathogenic/Likely pathogenic ★★ same condition
MCPH1 p.Gln386Ter Pathogenic/Likely pathogenic ★★ same condition
MCPH1 p.Gly245Ter Pathogenic/Likely pathogenic ★★ same condition
MCPH1 p.Leu542Ter Pathogenic/Likely pathogenic ★★ same condition
MCPH1 p.Ser72Leu Pathogenic/Likely pathogenic ★★ same condition
MCPH1 c.1935+6T>C 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/mcph1-p-cys371 (accessed [today's date]).

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