Is ENAM p.Lys124fs (c.372_382del) pathogenic?

ENAM p.Lys124fs (c.372382del) is classified Likely pathogenic in ENAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-21). Absent from gnomAD.

How common is ENAM p.Lys124fs (c.372_382del) in the general population?

ENAM p.Lys124fs (c.372_382del) is absent from gnomAD (gnomAD).

ENAM p.Lys124fs

c.372_382del · rs2545343550 · VCV2440040

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.5	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ENAM
Protein: p.Lys124fs
Coding: c.372_382del
MANE Select: NM_031889
dbSNP: rs2545343550
Type: Deletion
Location: chr4:70634468 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 36.63
Residue 124: the 'disordered' region

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

Similar variants

ENAM c.588+1del Pathogenic ★★ same type
ENAM p.Asp921fs Pathogenic/Likely pathogenic ★★ same type
ENAM p.Asn36fs Likely pathogenic ★ same type
ENAM p.Asn628fs Likely pathogenic ★ same type
ENAM p.Ser312fs Likely pathogenic ★ same type
ENAM c.123+3_123+6del Uncertain significance ★ same type
ENAM p.Phe1002fs Uncertain significance ★ 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/enam-p-lys124fs (accessed [today's date]).

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