Is ACTL9 p.Glu107Gln (c.319G>C) pathogenic?

ACTL9 p.Glu107Gln (c.319G>C) is classified Uncertain significance in ACTL9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). Very rare (popmax 0.00539%, nfe).

How common is ACTL9 p.Glu107Gln (c.319G>C) in the general population?

ACTL9 p.Glu107Gln (c.319G>C) is very rare (popmax 0.00539%, nfe) (gnomAD).

ACTL9 p.Glu107Gln

c.319G>C · rs781807703 · VCV2405096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00539%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.383	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.73, phastCons 0.96
Regional constraint	o/e 1.05	unconstrained · MANE · 1,247 bp · p 0.2 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00539% European (non-Finnish) · 61/1,131,378 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.00455% 69/1,516,206 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0086%	11,628
European (non-Finnish)grpmax	0.00539%	18,547
African / African-American	0.00278%	35,948
Admixed American	0.00219%	45,618

Remaining individuals 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: ACTL9
Protein: p.Glu107Gln
Coding: c.319G>C
MANE Select: NM_178525
dbSNP: rs781807703
Type: single nucleotide variant
Location: chr19:8698383 (GRCh38)
Gene constraint: LOEUF 1.575 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 87.56

Full ACTL9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTL9 p.Ala174Asp Uncertain significance ★ same type
ACTL9 p.Ala174Thr Uncertain significance ★ same type
ACTL9 p.Ala187Ser Uncertain significance ★ same type
ACTL9 p.Ala319Ser Uncertain significance ★ same type
ACTL9 p.Ala361Thr Uncertain significance ★ same type
ACTL9 p.Ala388Asp Uncertain significance ★ same type
ACTL9 p.Ala392Gly Uncertain significance ★ same type
ACTL9 p.Arg130Leu 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/actl9-p-glu107gln (accessed [today's date]).

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