Is KDF1 p.Ser137= (c.411C>T) pathogenic?

KDF1 p.Ser137= (c.411C>T) is classified Likely benign in KDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). Very rare (popmax 0.00267%, afr).

How common is KDF1 p.Ser137= (c.411C>T) in the general population?

KDF1 p.Ser137= (c.411C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

KDF1 p.Ser137=

c.411C>T · VCV3612628

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.188	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -4, phastCons 1
Overall
CADD	4.974	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,988 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000311% 5/1,609,628 alleles · very rare exomes 5/1,457,310 · genomes 0/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,494
South Asian	0.0022%	45,447
European (non-Finnish)	8.5e-05%	1,176,923

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.Ser137=
Coding: c.411C>T
MANE Select: NM_152365
Type: single nucleotide variant
Location: chr1:26951970 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 59.59
Residue 137: the 'disordered' region

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

Similar variants

KDF1 p.Ser137Arg Uncertain significance ★ ⚠ same residue
KDF1 p.Ser137Ile Uncertain significance ★ ⚠ same residue
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

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-ser137 (accessed [today's date]).

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