Is ACTB c.*124del pathogenic?

ACTB c.124del is classified Benign in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-10). Common (popmax 14.2%, amr) — too common for a highly-penetrant pathogenic allele.

ACTB c.*124del

Q: How common is ACTB c.*124del in the general population?

ACTB c.*124del is common (popmax 14.2%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs370106412 · VCV1272390

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 14.2%, amr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP -2.2, phastCons 0.99
Non-coding constraint	Z 0.06	1 kb window · o/e 1.00 · regional · uncalibrated
Overall
CADD	16.16	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	A-rich low complexity, segmental duplication · ambiguous alignment · reads may not map uniquely · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.2% Admixed American · 4,817/34,016 alleles

Filtering AF 13.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.7%

Overall 13.3% 150,679/1,134,546 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	15.7%	6
Admixed Americangrpmax	14.2%	7
European (non-Finnish)	13.5%	7
Remaining individualsnot grpmax-eligible	13.1%	8
Ashkenazi Jewishnot grpmax-eligible	13.1%	8
East Asian	12.5%	8
South Asian	11.4%	9
Middle Eastern	11.3%	9
African / African-American	9.36%	11
Amishnot grpmax-eligible	5.37%	19

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACTB
Coding: c.*124del
MANE Select: NM_001101
dbSNP: rs370106412
Type: Deletion
Location: chr7:5527624 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB

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

Similar variants

ACTB c.985-1_989del Likely pathogenic ★ same type
ACTB p.Asp11del Likely pathogenic ★ same type
ACTB p.Asp311fs Likely pathogenic ★ same type
ACTB p.Gly48fs Pathogenic ★ same type
ACTB p.Leu110fs Pathogenic ★ same type
ACTB p.Ser300_Met305del Likely pathogenic ★ same type
ACTB p.Ala181_Leu185del Uncertain significance ★ same type
ACTB p.Asp222_Phe223del 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/actb-c-star-124del (accessed [today's date]).

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