Is KDF1 p.Arg107= (c.321G>T) pathogenic?

KDF1 p.Arg107= (c.321G>T) is classified Likely benign in KDF1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-24). Very rare (popmax 0.00958%, nfe); Associated with KDF1-related disorder.

What condition is associated with KDF1 p.Arg107= (c.321G>T)?

KDF1 p.Arg107= (c.321G>T) is associated with KDF1-related disorder (ClinVar).

How common is KDF1 p.Arg107= (c.321G>T) in the general population?

KDF1 p.Arg107= (c.321G>T) is very rare (popmax 0.00958%, nfe) (gnomAD).

KDF1 p.Arg107=

c.321G>T · rs371561424 · VCV3043086

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00958%, nfe)

Conditions

KDF1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.028	GERP -1.3, phastCons 0.008
Overall
CADD	6.933	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00958% European (non-Finnish) · 113/1,179,912 alleles

Filtering AF 0.00809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0076%

Overall 0.00719% 116/1,613,316 alleles · very rare exomes 115/1,461,102 · genomes 1/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00958%	10,442
Remaining individualsnot grpmax-eligible	0.0048%	20,819

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: KDF1
Protein: p.Arg107=
Coding: c.321G>T
MANE Select: NM_152365
dbSNP: rs371561424
Type: single nucleotide variant
Location: chr1:26952060 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 59.59
Residue 107: a UniProt-annotated variant site (in)

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

Disease context

KDF1-related disorder

Similar variants

KDF1 p.Arg107Trp Benign ★★ same residue
KDF1 p.Arg107Gln Uncertain significance ★ ⚠ same residue
KDF1 p.Arg299= Likely benign same condition
KDF1 p.Cys91= Likely benign 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

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-arg107 (accessed [today's date]).

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