Is ACTL7A p.Pro387= (c.1161G>A) pathogenic?

ACTL7A p.Pro387= (c.1161G>A) is classified Likely benign in ACTL7A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-01). Ultra-rare (popmax 0.0666%, afr).

How common is ACTL7A p.Pro387= (c.1161G>A) in the general population?

ACTL7A p.Pro387= (c.1161G>A) is ultra-rare (popmax 0.0666%, afr) (gnomAD).

ACTL7A p.Pro387=

c.1161G>A · VCV3483756

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0666%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.4	GERP -3.9
Overall
CADD	0.421	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0666% African / African-American · 50/75,066 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0466%

Overall 0.0206% 332/1,614,192 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0666%	1,501
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.0217%	4,618
European (non-Finnish)	0.0213%	4,701
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,359

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.Pro387=
Coding: c.1161G>A
MANE Select: NM_006687
Type: single nucleotide variant
Location: chr9:108863483 (GRCh38)
Gene constraint: LOEUF 1.182 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.81 · 1 PDB
Residue 387: a UniProt-annotated variant site (in spgf86; likely pathogenic); a UniProt-annotated variant site (in spgf86; likely pathogenic; loss of protein expression in patient sperm)

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

Similar variants

ACTL7A p.Arg373His Likely pathogenic ★ same type
ACTL7A p.Gly402Ser Likely pathogenic ★ same type
ACTL7A p.Ala166Glu Uncertain significance ★ ⚠ same type
ACTL7A p.Ala166Val Uncertain significance ★ ⚠ same type
ACTL7A p.Ala190Asp Uncertain significance ★ ⚠ same type
ACTL7A p.Ala27Asp Uncertain significance ★ ⚠ same type
ACTL7A p.Ala86Gly Uncertain significance ★ ⚠ same type
ACTL7A p.Arg113Cys 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/actl7a-p-pro387 (accessed [today's date]).

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