Is MCPH1 p.Ser573= (c.1719C>T) pathogenic?

MCPH1 p.Ser573= (c.1719C>T) is classified Benign/Likely benign in MCPH1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.41%, afr); Associated with microcephaly 1, primary, autosomal recessive.

What condition is associated with MCPH1 p.Ser573= (c.1719C>T)?

MCPH1 p.Ser573= (c.1719C>T) is associated with microcephaly 1, primary, autosomal recessive (ClinVar).

How common is MCPH1 p.Ser573= (c.1719C>T) in the general population?

MCPH1 p.Ser573= (c.1719C>T) is low-frequency (popmax 4.41%, afr) (gnomAD).

MCPH1 p.Ser573=

c.1719C>T · rs35551093 · VCV158824

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.41%, afr)

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 -2	GERP -2.8
Overall
CADD	1.164	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.41% African / African-American · 3,309/75,046 alleles

Filtering AF 4.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.23%

Overall 0.249% 4,014/1,614,218 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.41%	23
Remaining individualsnot grpmax-eligible	0.4%	250
Middle Eastern	0.396%	253
Admixed American	0.363%	275
European (non-Finnish)	0.017%	5,871
South Asian	0.011%	9,109
Finnishnot grpmax-eligible	0.00312%	32,015

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.Ser573=
Coding: c.1719C>T
MANE Select: NM_024596
dbSNP: rs35551093
Type: single nucleotide variant
Location: chr8:6445441 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 9 PDB
Residue 573: 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.Ser573Phe 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-ser573 (accessed [today's date]).

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