Is KIF5C p.Pro4Ser (c.10C>T) pathogenic?

KIF5C p.Pro4Ser (c.10C>T) is classified Uncertain significance in KIF5C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). AlphaMissense: likely benign (0.1306); Very rare (popmax 0.00167%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KIF5C p.Pro4Ser (c.10C>T)?

KIF5C p.Pro4Ser (c.10C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KIF5C p.Pro4Ser (c.10C>T) in the general population?

KIF5C p.Pro4Ser (c.10C>T) is very rare (popmax 0.00167%, nfe) (gnomAD).

What do computational predictors say about KIF5C p.Pro4Ser (c.10C>T)?

AlphaMissense predicts likely benign (score 0.1306) — an in-silico prediction, not a clinical call.

KIF5C p.Pro4Ser

c.10C>T · VCV3864381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1306 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1306	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -4.82	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 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 86 kb · p 7.3e-29 · regional, not allelic
Overall
CADD	25.1	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 0.00167% European (non-Finnish) · 18/1,076,668 alleles

Filtering AF 0.00104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000862%

Overall 0.00132% 19/1,436,252 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00167%	59,815
African / African-American	0.00145%	68,816

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: KIF5C
Protein: p.Pro4Ser
Coding: c.10C>T
MANE Select: NM_004522
Type: single nucleotide variant
Location: chr2:148875627 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.70

Full KIF5C 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

KIF5C p.Pro4Thr Uncertain significance ★ ⚠ same residue
KIF5C p.Tyr47His Uncertain significance ★★ ⚠ same condition
KIF5C p.Asn19Ser Uncertain significance ★ ⚠ same condition
KIF5C p.Asn64Ser Uncertain significance ★ ⚠ same condition
KIF5C p.Asp27Asn Uncertain significance ★ ⚠ same condition
KIF5C p.Glu60Gly Uncertain significance ★ ⚠ same condition
KIF5C p.Gly42Arg Uncertain significance ★ ⚠ same condition
KIF5C p.Gly86Trp 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/kif5c-p-pro4ser (accessed [today's date]).

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