Is LITAF p.Lys159= (c.477G>A) pathogenic?

LITAF p.Lys159= (c.477G>A) is classified Conflicting classifications of pathogenicity in LITAF (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-21). Ultra-rare (popmax 0.0108%, nfe); Associated with Charcot-Marie-Tooth disease type 1C.

What condition is associated with LITAF p.Lys159= (c.477G>A)?

LITAF p.Lys159= (c.477G>A) is associated with Charcot-Marie-Tooth disease type 1C, Charcot-Marie-Tooth disease (ClinVar).

How common is LITAF p.Lys159= (c.477G>A) in the general population?

LITAF p.Lys159= (c.477G>A) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

How is Charcot-Marie-Tooth disease type 1C inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

LITAF p.Lys159=

c.477G>A · rs371453151 · VCV637892

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Conditions

Charcot-Marie-Tooth disease type 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.165	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.5	GERP 1.1, phastCons 1
Overall
CADD	10.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0108% European (non-Finnish) · 127/1,178,742 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00864%

Overall 0.00856% 138/1,612,154 alleles · ultra-rare exomes 131/1,459,956 · genomes 7/152,198 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0108%	9,281
African / African-American	0.00667%	14,992
Admixed American	0.00501%	19,971
Remaining individualsnot grpmax-eligible	0.0048%	20,815

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: LITAF
Protein: p.Lys159=
Coding: c.477G>A
MANE Select: NM_001136472
dbSNP: rs371453151
Type: single nucleotide variant
Location: chr16:11549646 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 70.60
Residue 159: the litaf domain

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

Disease context

Charcot-Marie-Tooth disease type 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease

For Charcot-Marie-Tooth disease type 1C (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

LITAF p.Ala111Gly Pathogenic ★★ same condition
LITAF p.Gly112Ser Pathogenic ★★ ⚠ same condition
LITAF p.Thr115Asn Pathogenic/Likely pathogenic ★★ same condition
LITAF c.220+4C>T Uncertain significance ★★ same condition
LITAF p.Ala129Val Uncertain significance ★★ ⚠ same condition
LITAF p.Ala140Thr Uncertain significance ★★ ⚠ same condition
LITAF p.Ala153Thr Uncertain significance ★★ ⚠ same condition
LITAF p.Ala153Val 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/litaf-p-lys159 (accessed [today's date]).

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