Is KANK1 p.Ala1237Val (c.3710C>T) pathogenic?

KANK1 p.Ala1237Val (c.3710C>T) is classified Uncertain significance in KANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely pathogenic (0.9843); Very rare (popmax 0.000124%).

How common is KANK1 p.Ala1237Val (c.3710C>T) in the general population?

KANK1 p.Ala1237Val (c.3710C>T) is very rare (popmax 0.000124%) (gnomAD).

What do computational predictors say about KANK1 p.Ala1237Val (c.3710C>T)?

AlphaMissense predicts likely pathogenic (score 0.9843) — an in-silico prediction, not a clinical call.

KANK1 p.Ala1237Val

c.3710C>T · rs1310303858 · VCV2004113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9843 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000124%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9843	likely pathogenic · top 4% in KANK1
REVEL	0.63	indeterminate
SaProt	LLR -13.61	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 68 kb · p 3.5e-62 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000124%

Overall 0.000124% 2/1,614,118 alleles · very rare exomes 2/1,461,776 · genomes 0/152,342 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
Finnishnot grpmax-eligible	0.00156%	64,018

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: KANK1
Protein: p.Ala1237Val
Coding: c.3710C>T
MANE Select: NM_015158
dbSNP: rs1310303858
Type: single nucleotide variant
Location: chr9:742218 (GRCh38)
Gene constraint: LOEUF 1.149 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.50 · 5 PDB
Residue 1237: the 'interaction with kif21a' region; an α-helix

Full KANK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KANK1 p.Ala1237fs Uncertain significance ★★ same residue
KANK1 c.2896+2T>G Uncertain significance ★★ same type
KANK1 p.Ala109Thr Uncertain significance ★★ ⚠ same type
KANK1 p.Ala1184= Uncertain significance ★★ same type
KANK1 p.Ala1203Val Uncertain significance ★★ ⚠ same type
KANK1 p.Ala1255Asp Uncertain significance ★★ ⚠ same type
KANK1 p.Ala228Gly Uncertain significance ★★ ⚠ same type
KANK1 p.Ala718Gly 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/kank1-p-ala1237val (accessed [today's date]).

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