Is LITAF p.Pro67Ser (c.199C>T) pathogenic?

LITAF p.Pro67Ser (c.199C>T) is classified Uncertain significance in LITAF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-18). AlphaMissense: likely benign (0.0711); Very rare (popmax 0.00446%, eas); Associated with Charcot-Marie-Tooth disease.

What condition is associated with LITAF p.Pro67Ser (c.199C>T)?

LITAF p.Pro67Ser (c.199C>T) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease type 1C (ClinVar).

How common is LITAF p.Pro67Ser (c.199C>T) in the general population?

LITAF p.Pro67Ser (c.199C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about LITAF p.Pro67Ser (c.199C>T)?

AlphaMissense predicts likely benign (score 0.0711) — an in-silico prediction, not a clinical call.

LITAF p.Pro67Ser

c.199C>T · rs2064271547 · VCV917347

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0711 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
AlphaMissense	0.0711	likely benign
REVEL	0.391	indeterminate
SaProt	LLR -7.57	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 0.79, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,090 bp · p 0.61 · regional, not allelic
Overall
CADD	19.55	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.00446% East Asian · 2/44,892 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000205% 3/1,461,748 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,446
European (non-Finnish)	8.47e-05%	1,179,942

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.Pro67Ser
Coding: c.199C>T
MANE Select: NM_001136472
dbSNP: rs2064271547
Type: single nucleotide variant
Location: chr16:11556532 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 70.60

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

Also linked: Charcot-Marie-Tooth disease type 1C

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-pro67ser (accessed [today's date]).

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