Is KANK4 p.Asp411= (c.1233C>T) pathogenic?

KANK4 p.Asp411= (c.1233C>T) is classified Likely benign in KANK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). Very rare (popmax 0.00667%, afr).

How common is KANK4 p.Asp411= (c.1233C>T) in the general population?

KANK4 p.Asp411= (c.1233C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

KANK4 p.Asp411=

c.1233C>T · VCV4752790

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, 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 -9.9	GERP -4.2
Overall
CADD	0.054	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,910 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00217% 35/1,614,030 alleles · very rare exomes 27/1,461,888 · genomes 8/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,982
European (non-Finnish)	0.00237%	42,144
Remaining individualsnot grpmax-eligible	0.0016%	62,490
Finnishnot grpmax-eligible	0.00156%	64,038

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.Asp411=
Coding: c.1233C>T
MANE Select: NM_181712
Type: single nucleotide variant
Location: chr1:62273871 (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

Similar variants

KANK4 p.Ala115Val Uncertain significance ★★ ⚠ same type
KANK4 p.Ala987Thr Uncertain significance ★★ ⚠ same type
KANK4 p.Arg336Met Uncertain significance ★★ ⚠ same type
KANK4 p.Arg471Cys Uncertain significance ★★ ⚠ same type
KANK4 p.Arg653Cys Uncertain significance ★★ ⚠ same type
KANK4 p.Arg790Gln Uncertain significance ★★ ⚠ same type
KANK4 p.Asp266Gly Uncertain significance ★★ ⚠ same type
KANK4 p.Asp459Val 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/kank4-p-asp411 (accessed [today's date]).

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