Is ACTL7A p.Glu50fs (c.149_150del) pathogenic?

ACTL7A p.Glu50fs (c.149150del) is classified Pathogenic in ACTL7A (ClinVar, No assertion criteria, 1 submitter). Ultra-rare (popmax 0.0209%, sas); Associated with Male infertility with normal semen parameters.

What condition is associated with ACTL7A p.Glu50fs (c.149_150del)?

ACTL7A p.Glu50fs (c.149_150del) is associated with Male infertility with normal semen parameters (ClinVar).

How common is ACTL7A p.Glu50fs (c.149_150del) in the general population?

ACTL7A p.Glu50fs (c.149_150del) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

ACTL7A p.Glu50fs

c.149_150del · rs745719906 · VCV1343822

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Conditions

Male infertility with normal semen parameters

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.12	GERP -1.8
Overall
CADD	19.68	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% South Asian · 19/91,078 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00143% 23/1,613,960 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,794
Remaining individualsnot grpmax-eligible	0.0064%	15,622

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: ACTL7A
Protein: p.Glu50fs
Coding: c.149_150del
MANE Select: NM_006687
dbSNP: rs745719906
Type: Microsatellite
Location: chr9:108862469 (GRCh38)
Gene constraint: LOEUF 1.182 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.81 · 1 PDB
Residue 50: the 'disordered' region; the 'required for interaction with tes' region; a UniProt-annotated variant site (in spgf86; likely pathogenic)

Full ACTL7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Male infertility with normal semen parameters

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/actl7a-p-glu50fs (accessed [today's date]).

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