Is KLC2 p.Asp504Val (c.1511A>T) pathogenic?

KLC2 p.Asp504Val (c.1511A>T) is classified Uncertain significance in KLC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-18). AlphaMissense: likely benign (0.1619); Absent from gnomAD v4.1.

How common is KLC2 p.Asp504Val (c.1511A>T) in the general population?

KLC2 p.Asp504Val (c.1511A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KLC2 p.Asp504Val (c.1511A>T)?

AlphaMissense predicts likely benign (score 0.1619) — an in-silico prediction, not a clinical call.

KLC2 p.Asp504Val

c.1511A>T · rs1590874557 · VCV2035964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1619 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1619	likely benign
REVEL	0.408	indeterminate
SaProt	LLR -6.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP -0.94, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 8,358 bp · p 1.4e-14 · regional, not allelic
Overall
CADD	21.3	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

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: KLC2
Protein: p.Asp504Val
Coding: c.1511A>T
MANE Select: NM_001318734
dbSNP: rs1590874557
Type: single nucleotide variant
Location: chr11:66265921 (GRCh38)
Gene constraint: LOEUF 0.616 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.79 · 2 PDB
Residue 504: the 'disordered' region

Full KLC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KLC2 p.Arg110His Uncertain significance ★★ ⚠ same type
KLC2 p.Arg418Gln Uncertain significance ★★ ⚠ same type
KLC2 p.Arg418Trp Uncertain significance ★★ ⚠ same type
KLC2 p.Arg479His Uncertain significance ★★ ⚠ same type
KLC2 p.Arg509Gln Uncertain significance ★★ ⚠ same type
KLC2 p.Arg616Gln Uncertain significance ★★ ⚠ same type
KLC2 p.Arg96Gln Uncertain significance ★★ same type
KLC2 p.Asn170Ser 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/klc2-p-asp504val (accessed [today's date]).

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