Is KDF1 p.Arg146Pro (c.437G>C) pathogenic?

KDF1 p.Arg146Pro (c.437G>C) is classified Uncertain significance in KDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: likely benign (0.1239); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with KDF1 p.Arg146Pro (c.437G>C)?

KDF1 p.Arg146Pro (c.437G>C) is associated with Inborn genetic diseases (ClinVar).

How common is KDF1 p.Arg146Pro (c.437G>C) in the general population?

KDF1 p.Arg146Pro (c.437G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDF1 p.Arg146Pro (c.437G>C)?

AlphaMissense predicts likely benign (score 0.1239) — an in-silico prediction, not a clinical call.

KDF1 p.Arg146Pro

c.437G>C · rs765268716 · VCV2560116

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1239 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1239	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -5.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.89, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 711 bp · p 0.9 · regional, not allelic
Overall
CADD	21.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KDF1
Protein: p.Arg146Pro
Coding: c.437G>C
MANE Select: NM_152365
dbSNP: rs765268716
Type: single nucleotide variant
Location: chr1:26951944 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 59.59
Residue 146: the 'disordered' region

Full KDF1 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

KDF1 p.Arg319Cys Uncertain significance ★★ ⚠ same condition
KDF1 p.Arg87Gln Uncertain significance ★★ ⚠ same condition
KDF1 p.Glu190Lys Uncertain significance ★★ ⚠ same condition
KDF1 p.Ser380Pro Uncertain significance ★★ ⚠ same condition
KDF1 p.Ser388Leu Uncertain significance ★★ ⚠ same condition
KDF1 p.Ala104Thr Uncertain significance ★ ⚠ same condition
KDF1 p.Ala123Val Uncertain significance ★ ⚠ same condition
KDF1 p.Ala184Val 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/kdf1-p-arg146pro (accessed [today's date]).

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