Is ANKRD31 p.Val395fs (c.1184_1187del) pathogenic?

ANKRD31 p.Val395fs (c.11841187del) is classified Likely pathogenic in ANKRD31 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). Very rare (popmax 0.0027%, nfe); Associated with inherited primary ovarian failure.

What condition is associated with ANKRD31 p.Val395fs (c.1184_1187del)?

ANKRD31 p.Val395fs (c.1184_1187del) is associated with inherited primary ovarian failure (ClinVar).

How common is ANKRD31 p.Val395fs (c.1184_1187del) in the general population?

ANKRD31 p.Val395fs (c.1184_1187del) is very rare (popmax 0.0027%, nfe) (gnomAD).

ANKRD31 p.Val395fs

c.1184_1187del · VCV3773785

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0027%, nfe)

Conditions

inherited primary ovarian failure

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 8 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -0.47, phastCons 0.003
Overall
CADD	23.0	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 0.0027% European (non-Finnish) · 31/1,146,772 alleles

Filtering AF 0.00194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00169%

Overall 0.00208% 32/1,537,070 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0027%	36,993
Admixed American	0.00196%	50,960

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: ANKRD31
Protein: p.Val395fs
Coding: c.1184_1187del
MANE Select: NM_001372053
Type: Deletion
Location: chr5:75193422 (GRCh38)
Gene constraint: LOEUF 0.844 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.08

Full ANKRD31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited primary ovarian failure — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/ankrd31-p-val395fs (accessed [today's date]).

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