Is MCPH1 p.Val71Ile (c.211G>A) pathogenic?

MCPH1 p.Val71Ile (c.211G>A) is classified Uncertain significance in MCPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.2006); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with MCPH1 p.Val71Ile (c.211G>A)?

MCPH1 p.Val71Ile (c.211G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MCPH1 p.Val71Ile (c.211G>A) in the general population?

MCPH1 p.Val71Ile (c.211G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about MCPH1 p.Val71Ile (c.211G>A)?

AlphaMissense predicts likely benign (score 0.2006) — an in-silico prediction, not a clinical call.

MCPH1 p.Val71Ile

c.211G>A · rs1301304396 · VCV2213298

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2006	likely benign
REVEL	0.65	pathogenic-leaning
SaProt	LLR -9.85	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 2.5, phastCons 1
Regional constraint	o/e 1.49	unconstrained · MANE · 236 kb · p 2.4e-54 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,866 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000682% 11/1,613,612 alleles · very rare exomes 8/1,461,680 · genomes 3/151,932 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,433
European (non-Finnish)	0.000763%	131,096

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.Val71Ile
Coding: c.211G>A
MANE Select: NM_024596
dbSNP: rs1301304396
Type: single nucleotide variant
Location: chr8:6414861 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 9 PDB
Residue 71: the brct 1 domain; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MCPH1 c.1935+6T>C Uncertain significance ★★ same condition
MCPH1 p.Ala401Val Uncertain significance ★★ ⚠ same condition
MCPH1 p.Ala404Val Uncertain significance ★★ ⚠ same condition
MCPH1 p.Arg373Thr Uncertain significance ★★ ⚠ same condition
MCPH1 p.Arg379Ile Uncertain significance ★★ ⚠ same condition
MCPH1 p.Arg703His Uncertain significance ★★ ⚠ same condition
MCPH1 p.Arg785Trp Uncertain significance ★★ ⚠ same condition
MCPH1 p.Asp758Asn 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-val71ile (accessed [today's date]).

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