Is KEL p.Pro402Thr (c.1204C>A) pathogenic?

KEL p.Pro402Thr (c.1204C>A) is classified Uncertain significance in KEL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.076); Very rare (popmax 0.00687%, nfe).

How common is KEL p.Pro402Thr (c.1204C>A) in the general population?

KEL p.Pro402Thr (c.1204C>A) is very rare (popmax 0.00687%, nfe) (gnomAD).

What do computational predictors say about KEL p.Pro402Thr (c.1204C>A)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

KEL p.Pro402Thr

c.1204C>A · rs779858065 · VCV3113946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00687%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 21 kb · p 0.95 · regional, not allelic
Overall
CADD	19.15	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00687% European (non-Finnish) · 81/1,178,700 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00509% 82/1,611,820 alleles · very rare exomes 76/1,459,650 · genomes 6/152,170 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00687%	14,552
Remaining individualsnot grpmax-eligible	0.0016%	62,404

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: KEL
Protein: p.Pro402Thr
Coding: c.1204C>A
MANE Select: NM_000420
dbSNP: rs779858065
Type: single nucleotide variant
Location: chr7:142946317 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.46
Residue 402: the peptidase m13 domain

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

Similar variants

KEL p.Pro375Thr Uncertain significance ★★ ⚠ same type
KEL p.Arg516= Benign ★★ same type
KEL p.Leu335= Likely benign ★★ same type
KEL p.Leu597Pro Benign ★★ same type
KEL p.Phe324= Benign ★★ same type
KEL c.400+1G>A Pathogenic ★ same type
KEL p.Ala148Gly Uncertain significance ★ ⚠ same type
KEL p.Ala311Asp 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/kel-p-pro402thr (accessed [today's date]).

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