Is LITAF p.Pro17= (c.51A>G) pathogenic?

LITAF p.Pro17= (c.51A>G) is classified Likely benign in LITAF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-19). Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with LITAF p.Pro17= (c.51A>G)?

LITAF p.Pro17= (c.51A>G) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 1C (ClinVar).

How common is LITAF p.Pro17= (c.51A>G) in the general population?

LITAF p.Pro17= (c.51A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

LITAF p.Pro17=

c.51A>G · rs751525365 · VCV532705

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -3.9
Overall
CADD	0.685	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,614,184 alleles · ultra-rare exomes 5/1,461,890 · genomes 0/152,294 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
African / African-American	0.00133%	75,036
European (non-Finnish)	0.000254%	393,349

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.Pro17=
Coding: c.51A>G
MANE Select: NM_001136472
dbSNP: rs751525365
Type: single nucleotide variant
Location: chr16:11556680 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 70.60
Residue 17: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

LITAF p.Pro17Gln Uncertain significance ★ ⚠ same residue
LITAF p.Pro17Leu Conflicting classifications of pathogenicity ★ ⚠ 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.Ala129Val Uncertain significance ★★ ⚠ same condition
LITAF p.Ala140Thr 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-pro17 (accessed [today's date]).

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