Is LITAF p.Ala129= (c.387G>A) pathogenic?

LITAF p.Ala129= (c.387G>A) is classified Likely benign in LITAF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-24). Very rare (popmax 0.0044%, sas); Associated with Charcot-Marie-Tooth disease type 1C.

What condition is associated with LITAF p.Ala129= (c.387G>A)?

LITAF p.Ala129= (c.387G>A) is associated with Charcot-Marie-Tooth disease type 1C (ClinVar).

How common is LITAF p.Ala129= (c.387G>A) in the general population?

LITAF p.Ala129= (c.387G>A) is very rare (popmax 0.0044%, sas) (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.Ala129=

c.387G>A · rs777363288 · VCV2080157

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

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	0.241	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.9	GERP -4.2
Overall
CADD	0.723	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0044% South Asian · 4/90,810 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.000806% 13/1,612,478 alleles · very rare exomes 9/1,460,334 · genomes 4/152,144 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,703
Finnishnot grpmax-eligible	0.00313%	31,962
East Asian	0.00223%	44,832
Admixed American	0.00167%	59,772
European (non-Finnish)	0.000424%	235,854

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.Ala129=
Coding: c.387G>A
MANE Select: NM_001136472
dbSNP: rs777363288
Type: single nucleotide variant
Location: chr16:11549736 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 70.60
Residue 129: the litaf domain; the 'membrane-binding amphipathic helix' region

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.Ala129Val Uncertain significance ★★ ⚠ same residue
LITAF p.Ala129Thr Uncertain significance ★ ⚠ 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.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-ala129 (accessed [today's date]).

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