Is LITAF p.Pro51Ser (c.151C>T) pathogenic?

LITAF p.Pro51Ser (c.151C>T) is classified Conflicting classifications of pathogenicity in LITAF (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0829); Ultra-rare (popmax 0.0417%, amr); Associated with Inborn genetic diseases.

What condition is associated with LITAF p.Pro51Ser (c.151C>T)?

LITAF p.Pro51Ser (c.151C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 1C (ClinVar).

How common is LITAF p.Pro51Ser (c.151C>T) in the general population?

LITAF p.Pro51Ser (c.151C>T) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

What do computational predictors say about LITAF p.Pro51Ser (c.151C>T)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

LITAF p.Pro51Ser

c.151C>T · rs752978718 · VCV404113

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.403	indeterminate
SaProt	LLR -7.47	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	GERP 0.79, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,090 bp · p 0.61 · regional, not allelic
Overall
CADD	20.9	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 0.0417% Admixed American · 25/59,994 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00204% 33/1,614,064 alleles · ultra-rare exomes 31/1,461,892 · genomes 2/152,172 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,400
African / African-American	0.00133%	74,916
European (non-Finnish)	0.000593%	168,577

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.Pro51Ser
Coding: c.151C>T
MANE Select: NM_001136472
dbSNP: rs752978718
Type: single nucleotide variant
Location: chr16:11556580 (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

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.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-pro51ser (accessed [today's date]).

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