Is ASPM p.Phe371Leu (c.1113C>G) pathogenic?

ASPM p.Phe371Leu (c.1113C>G) is classified Uncertain significance in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-16). AlphaMissense: likely pathogenic (0.8768); Very rare (popmax 6.85e-05%).

How common is ASPM p.Phe371Leu (c.1113C>G) in the general population?

ASPM p.Phe371Leu (c.1113C>G) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about ASPM p.Phe371Leu (c.1113C>G)?

AlphaMissense predicts likely pathogenic (score 0.8768) — an in-silico prediction, not a clinical call.

ASPM p.Phe371Leu

c.1113C>G · rs2527404137 · VCV1800498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8768 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.8768	likely pathogenic · top 2% in ASPM
REVEL	0.215	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP -3.7, phastCons 0.063
Regional constraint	o/e 1.09	unconstrained · MANE · 3,369 bp · p 0.063 · regional, not allelic
Overall
CADD	14.54	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 6.85e-05%

Overall 6.85e-05% 1/1,460,600 alleles · very rare

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: ASPM
Protein: p.Phe371Leu
Coding: c.1113C>G
MANE Select: NM_018136
dbSNP: rs2527404137
Type: single nucleotide variant
Location: chr1:197143139 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 371: the 'sufficient for interaction with katna1:katnb1' region

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

Similar variants

ASPM c.2419+2T>C Pathogenic/Likely pathogenic ★★ same type
ASPM c.2488-1G>C Pathogenic/Likely pathogenic ★★ same type
ASPM c.2936+5G>A Likely pathogenic ★★ same type
ASPM c.3082+1G>C Pathogenic/Likely pathogenic ★★ same type
ASPM c.9084+5G>A Likely pathogenic ★★ same type
ASPM p.Arg1019Ter Pathogenic ★★ same type
ASPM p.Arg1271Ter Pathogenic ★★ same type
ASPM p.Arg1392Ter Pathogenic ★★ same type

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/aspm-p-phe371leu (accessed [today's date]).

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