Is KDF1 p.Pro143Ser (c.427C>T) pathogenic?

KDF1 p.Pro143Ser (c.427C>T) is classified Uncertain significance in KDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.0876); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with KDF1 p.Pro143Ser (c.427C>T)?

KDF1 p.Pro143Ser (c.427C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KDF1 p.Pro143Ser (c.427C>T) in the general population?

KDF1 p.Pro143Ser (c.427C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about KDF1 p.Pro143Ser (c.427C>T)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

KDF1 p.Pro143Ser

c.427C>T · VCV4622639

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -6.45	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 6.5	GERP 0.97, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 711 bp · p 0.9 · regional, not allelic
Overall
CADD	22.0	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 0.00267% African / African-American · 2/74,786 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,606,522 alleles · very rare exomes 1/1,454,330 · genomes 1/152,192 · joint denominator

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.Pro143Ser
Coding: c.427C>T
MANE Select: NM_152365
Type: single nucleotide variant
Location: chr1:26951954 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.85 (gnomAD)
Structure: AlphaFold pLDDT 59.59
Residue 143: 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-pro143ser (accessed [today's date]).

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