Is KDF1 p.Arg307Pro (c.920G>C) pathogenic?

KDF1 p.Arg307Pro (c.920G>C) is classified Uncertain significance in KDF1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9928); Absent from gnomAD v4.1; Associated with tooth agenesis.

What condition is associated with KDF1 p.Arg307Pro (c.920G>C)?

KDF1 p.Arg307Pro (c.920G>C) is associated with tooth agenesis (ClinVar).

How common is KDF1 p.Arg307Pro (c.920G>C) in the general population?

KDF1 p.Arg307Pro (c.920G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KDF1 p.Arg307Pro (c.920G>C)?

AlphaMissense predicts likely pathogenic (score 0.9928) — an in-silico prediction, not a clinical call.

KDF1 p.Arg307Pro

c.920G>C · rs1306524391 · VCV1301903

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9928 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

tooth agenesis

Computational evidence

Protein change
AlphaMissense	0.9928	likely pathogenic · top 6% in KDF1
REVEL	0.281	benign-leaning
SaProt	LLR -5.83	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 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 1,596 bp · p 1.5e-06 · regional, not allelic
Overall
CADD	33.0	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

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.Arg307Pro
Coding: c.920G>C
MANE Select: NM_152365
dbSNP: rs1306524391
Type: single nucleotide variant
Location: chr1:26951461 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 59.59
Residue 307: the 'disordered' region

Full KDF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tooth agenesis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDF1 p.Ile243Leu Likely pathogenic ★ ⚠ same condition
KDF1 p.Arg319Cys Uncertain significance ★★ ⚠ same type
KDF1 p.Arg3His Uncertain significance ★★ ⚠ same type
KDF1 p.Arg87Gln Uncertain significance ★★ ⚠ same type
KDF1 p.Glu190Lys Uncertain significance ★★ ⚠ same type
KDF1 p.Ser380Pro Uncertain significance ★★ ⚠ same type
KDF1 p.Ser388Leu Uncertain significance ★★ ⚠ same type
KDF1 c.1040-6C>T Benign/Likely benign ★★ 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/kdf1-p-arg307pro (accessed [today's date]).

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