Is LITAF p.Ile103= (c.309C>T) pathogenic?

LITAF p.Ile103= (c.309C>T) is classified Likely benign in LITAF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-23). Ultra-rare (popmax 0.0165%, mid); Associated with Charcot-Marie-Tooth disease type 1C.

What condition is associated with LITAF p.Ile103= (c.309C>T)?

LITAF p.Ile103= (c.309C>T) is associated with Charcot-Marie-Tooth disease type 1C (ClinVar).

How common is LITAF p.Ile103= (c.309C>T) in the general population?

LITAF p.Ile103= (c.309C>T) is ultra-rare (popmax 0.0165%, mid) (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.Ile103=

c.309C>T · VCV3705386

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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	<0.2	all four deltas below 0.2 · G>C here scores Δ0.84 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.3	GERP -3.6
Overall
CADD	9.819	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000958% 14/1,461,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.00266%	37,524
Remaining individualsnot grpmax-eligible	0.0016%	62,500
South Asian	0.0011%	91,072
European (non-Finnish)	0.000763%	131,113

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.Ile103=
Coding: c.309C>T
MANE Select: NM_001136472
Type: single nucleotide variant
Location: chr16:11553601 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 70.60
Residue 103: 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

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-ile103 (accessed [today's date]).

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