Is CS p.Lys14Glu (c.40A>G) pathogenic?

CS p.Lys14Glu (c.40A>G) is classified Uncertain significance in CS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). AlphaMissense: likely benign (0.1197); Absent from gnomAD v4.1.

How common is CS p.Lys14Glu (c.40A>G) in the general population?

CS p.Lys14Glu (c.40A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CS p.Lys14Glu (c.40A>G)?

AlphaMissense predicts likely benign (score 0.1197) — an in-silico prediction, not a clinical call.

CS p.Lys14Glu

c.40A>G · VCV4007275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1197 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,567,740)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1197	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -8.84	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 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 14 kb · p 0.074 · regional, not allelic
Overall
CADD	24.6	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

No allele count reported in gnomAD v4.1 (AN 1,567,740). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CS
Protein: p.Lys14Glu
Coding: c.40A>G
MANE Select: NM_004077
Type: single nucleotide variant
Location: chr12:56300162 (GRCh38)
Gene constraint: LOEUF 0.356 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.56 · 11 PDB

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

Similar variants

CS p.Leu257= Benign ★★ same type
CS p.Phe96= Benign ★★ same type
CS p.Ala2Gly Uncertain significance ★ ⚠ same type
CS p.Ala8Ser Uncertain significance ★ ⚠ same type
CS p.Arg183Gly Uncertain significance ★ ⚠ same type
CS p.Arg191Gln Uncertain significance ★ ⚠ same type
CS p.Arg218Gln Uncertain significance ★ ⚠ same type
CS p.Arg329Gln 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/cs-p-lys14glu (accessed [today's date]).

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