Is KATNB1 p.Ser49Pro (c.145T>C) pathogenic?

KATNB1 p.Ser49Pro (c.145T>C) is classified Uncertain significance in KATNB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-18). AlphaMissense: likely pathogenic (0.7956); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KATNB1 p.Ser49Pro (c.145T>C)?

KATNB1 p.Ser49Pro (c.145T>C) is associated with Inborn genetic diseases (ClinVar).

How common is KATNB1 p.Ser49Pro (c.145T>C) in the general population?

KATNB1 p.Ser49Pro (c.145T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about KATNB1 p.Ser49Pro (c.145T>C)?

AlphaMissense predicts likely pathogenic (score 0.7956) — an in-silico prediction, not a clinical call.

KATNB1 p.Ser49Pro

c.145T>C · rs2506891736 · VCV2290028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7956 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7956	likely pathogenic
REVEL	0.264	benign-leaning
SaProt	LLR -9.62	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 16 kb · p 4.3e-08 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,884 alleles

Overall 6.84e-05% 1/1,461,270 alleles · very rare

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: KATNB1
Protein: p.Ser49Pro
Coding: c.145T>C
MANE Select: NM_005886
dbSNP: rs2506891736
Type: single nucleotide variant
Location: chr16:57741791 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.58
Residue 49: the 'interaction with centrosomes' region; the 'interaction with dynein' region

Full KATNB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KATNB1 p.Ala121Val Uncertain significance ★★ ⚠ same condition
KATNB1 p.Ala411Thr Uncertain significance ★★ ⚠ same condition
KATNB1 p.Ala652Asp Uncertain significance ★★ ⚠ same condition
KATNB1 p.Arg304Cys Uncertain significance ★★ ⚠ same condition
KATNB1 p.Arg34Gln Uncertain significance ★★ ⚠ same condition
KATNB1 p.Arg617Gln Uncertain significance ★★ ⚠ same condition
KATNB1 p.Arg645Cys Uncertain significance ★★ same condition
KATNB1 p.Gln478His 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/katnb1-p-ser49pro (accessed [today's date]).

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