Is LITAF p.Thr49= (c.147G>A) pathogenic?

LITAF p.Thr49= (c.147G>A) is classified Likely benign in LITAF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-22). Ultra-rare (popmax 0.012%, nfe); Associated with Charcot-Marie-Tooth disease type 1C.

What condition is associated with LITAF p.Thr49= (c.147G>A)?

LITAF p.Thr49= (c.147G>A) is associated with Charcot-Marie-Tooth disease type 1C (ClinVar).

How common is LITAF p.Thr49= (c.147G>A) in the general population?

LITAF p.Thr49= (c.147G>A) is ultra-rare (popmax 0.012%, 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.Thr49=

c.147G>A · rs145659732 · VCV317786

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.2
Overall
CADD	0.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% European (non-Finnish) · 142/1,180,032 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0098%

Overall 0.00973% 157/1,614,132 alleles · ultra-rare exomes 148/1,461,892 · genomes 9/152,240 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.012%	8,310
Remaining individualsnot grpmax-eligible	0.0112%	8,930
South Asian	0.00329%	30,359
African / African-American	0.00267%	37,516
East Asian	0.00223%	44,864
Admixed American	0.00167%	60,002
Finnishnot grpmax-eligible	0.00156%	64,034

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.Thr49=
Coding: c.147G>A
MANE Select: NM_001136472
dbSNP: rs145659732
Type: single nucleotide variant
Location: chr16:11556584 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 70.60
Residue 49: a UniProt-annotated variant site (in cmt1c)

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

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.Thr49Met Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-thr49 (accessed [today's date]).

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