Is KANK4 p.Pro313= (c.939G>A) pathogenic?

KANK4 p.Pro313= (c.939G>A) is classified Likely benign in KANK4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-15). Rare (popmax 0.181%, mid); Associated with KANK4-related disorder.

What condition is associated with KANK4 p.Pro313= (c.939G>A)?

KANK4 p.Pro313= (c.939G>A) is associated with KANK4-related disorder (ClinVar).

How common is KANK4 p.Pro313= (c.939G>A) in the general population?

KANK4 p.Pro313= (c.939G>A) is rare (popmax 0.181%, mid) (gnomAD).

KANK4 p.Pro313=

c.939G>A · rs559482425 · VCV3041254

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.181%, mid)

Conditions

KANK4-related disorder

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 -8	GERP -4.2
Overall
CADD	0.972	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.181% Middle Eastern · 11/6,062 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.00434% 70/1,614,114 alleles · rare exomes 55/1,461,872 · genomes 15/152,242 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.181%	551
Remaining individualsnot grpmax-eligible	0.0176%	5,683
Admixed American	0.00666%	15,004
South Asian	0.00659%	15,180
East Asian	0.00446%	22,438
African / African-American	0.004%	25,007
European (non-Finnish)	0.0028%	35,758

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: KANK4
Protein: p.Pro313=
Coding: c.939G>A
MANE Select: NM_181712
dbSNP: rs559482425
Type: single nucleotide variant
Location: chr1:62274165 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.17

Full KANK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KANK4-related disorder

Similar variants

KANK4 p.Pro313Leu Uncertain significance ★ ⚠ same residue
KANK4 p.Arg471Cys Uncertain significance ★★ ⚠ same condition
KANK4 p.Asp692Asn Uncertain significance ★★ ⚠ same condition
KANK4 p.Met977Lys Uncertain significance ★★ ⚠ same condition
KANK4 p.Pro625Leu Uncertain significance ★★ ⚠ same condition
KANK4 p.Arg122Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
KANK4 p.His420Arg Uncertain significance ★ ⚠ same condition
KANK4 p.Leu182Gln Uncertain significance ★ ⚠ same condition

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/kank4-p-pro313 (accessed [today's date]).

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