Is ASPM p.Phe124Leu (c.370T>C) pathogenic?

ASPM p.Phe124Leu (c.370T>C) is classified Uncertain significance in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely pathogenic (0.9533); Absent from gnomAD v4.1.

How common is ASPM p.Phe124Leu (c.370T>C) in the general population?

ASPM p.Phe124Leu (c.370T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPM p.Phe124Leu (c.370T>C)?

AlphaMissense predicts likely pathogenic (score 0.9533) — an in-silico prediction, not a clinical call.

ASPM p.Phe124Leu

c.370T>C · rs764255993 · VCV1360998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9533 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.9533	likely pathogenic · top 1% in ASPM
REVEL	0.189	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 9.4	GERP 1.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,369 bp · p 0.063 · regional, not allelic
Overall
CADD	23.1	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

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: ASPM
Protein: p.Phe124Leu
Coding: c.370T>C
MANE Select: NM_018136
dbSNP: rs764255993
Type: single nucleotide variant
Location: chr1:197144028 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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-phe124leu (accessed [today's date]).

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