Is MCPH1 p.Phe763Ser (c.2288T>C) pathogenic?

MCPH1 p.Phe763Ser (c.2288T>C) is classified Uncertain significance in MCPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-06-26). AlphaMissense: likely pathogenic (0.9157); Absent from gnomAD v4.1; Associated with microcephaly 1, primary, autosomal recessive.

What condition is associated with MCPH1 p.Phe763Ser (c.2288T>C)?

MCPH1 p.Phe763Ser (c.2288T>C) is associated with microcephaly 1, primary, autosomal recessive (ClinVar).

How common is MCPH1 p.Phe763Ser (c.2288T>C) in the general population?

MCPH1 p.Phe763Ser (c.2288T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MCPH1 p.Phe763Ser (c.2288T>C)?

AlphaMissense predicts likely pathogenic (score 0.9157) — an in-silico prediction, not a clinical call.

MCPH1 p.Phe763Ser

c.2288T>C · rs587783738 · VCV158850

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9157 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 1, primary, autosomal recessive

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9157	likely pathogenic
REVEL	0.794	moderately pathogenic-leaning
SaProt	LLR -12.93	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.1	GERP 2, phastCons 1
Regional constraint	o/e 1.49	unconstrained · MANE · 236 kb · p 2.4e-54 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MCPH1
Protein: p.Phe763Ser
Coding: c.2288T>C
MANE Select: NM_024596
dbSNP: rs587783738
Type: single nucleotide variant
Location: chr8:6621527 (GRCh38)

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

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-phe763ser (accessed [today's date]).

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