Is LITAF p.Pro73Ser (c.217C>T) pathogenic?

LITAF p.Pro73Ser (c.217C>T) is classified Likely benign in LITAF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-12). AlphaMissense: likely benign (0.0975); Rare (popmax 0.165%, sas); Associated with Charcot-Marie-Tooth disease type 1C.

What condition is associated with LITAF p.Pro73Ser (c.217C>T)?

LITAF p.Pro73Ser (c.217C>T) is associated with Charcot-Marie-Tooth disease type 1C (ClinVar).

How common is LITAF p.Pro73Ser (c.217C>T) in the general population?

LITAF p.Pro73Ser (c.217C>T) is rare (popmax 0.165%, 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.

What do computational predictors say about LITAF p.Pro73Ser (c.217C>T)?

AlphaMissense predicts likely benign (score 0.0975) — an in-silico prediction, not a clinical call.

LITAF p.Pro73Ser

c.217C>T · rs540238627 · VCV2904344

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0975 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.165%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 1C

Computational evidence

Protein change
AlphaMissense	0.0975	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP -3, phastCons 0.003
Regional constraint	o/e 0.97	unconstrained · MANE · 7,090 bp · p 0.61 · regional, not allelic
Overall
CADD	14.57	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% South Asian · 150/91,062 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.00955% 154/1,612,932 alleles · rare exomes 142/1,460,582 · genomes 12/152,350 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.165%	607
Remaining individualsnot grpmax-eligible	0.0048%	20,817
European (non-Finnish)	8.48e-05%	1,178,984

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.Pro73Ser
Coding: c.217C>T
MANE Select: NM_001136472
dbSNP: rs540238627
Type: single nucleotide variant
Location: chr16:11556514 (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 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-pro73ser (accessed [today's date]).

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