Is LITAF p.Ala140Pro (c.418G>C) pathogenic?

LITAF p.Ala140Pro (c.418G>C) is classified Uncertain significance in LITAF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-14). AlphaMissense: likely pathogenic (0.7384); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease.

What condition is associated with LITAF p.Ala140Pro (c.418G>C)?

LITAF p.Ala140Pro (c.418G>C) is associated with Charcot-Marie-Tooth disease (ClinVar).

How common is LITAF p.Ala140Pro (c.418G>C) in the general population?

LITAF p.Ala140Pro (c.418G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LITAF p.Ala140Pro (c.418G>C)?

AlphaMissense predicts likely pathogenic (score 0.7384) — an in-silico prediction, not a clinical call.

LITAF p.Ala140Pro

c.418G>C · rs754821950 · VCV694878

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7384 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
AlphaMissense	0.7384	likely pathogenic
REVEL	0.663	pathogenic-leaning
SaProt	LLR -10.61	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,090 bp · p 0.61 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LITAF
Protein: p.Ala140Pro
Coding: c.418G>C
MANE Select: NM_001136472
dbSNP: rs754821950
Type: single nucleotide variant
Location: chr16:11549705 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 70.60
Residue 140: the litaf domain

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

Disease context

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

Similar variants

LITAF p.Ala140Thr Uncertain significance ★★ ⚠ same residue
LITAF p.Ala140= Likely benign ★ same residue
LITAF p.Ala111Gly Pathogenic ★★ same condition
LITAF p.Gly112Ser Pathogenic ★★ ⚠ same condition
LITAF p.Arg160His Uncertain significance ★★ ⚠ same condition
LITAF p.Arg90His Uncertain significance ★★ ⚠ same condition
LITAF p.Leu124Pro Uncertain significance ★★ ⚠ same condition
LITAF p.Pro67Ser 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-ala140pro (accessed [today's date]).

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