Is LITAF p.Ala9= (c.27G>A) pathogenic?

LITAF p.Ala9= (c.27G>A) is classified Benign/Likely benign in LITAF (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-01). Ultra-rare (popmax 0.0111%, eas); Associated with Inborn genetic diseases.

What condition is associated with LITAF p.Ala9= (c.27G>A)?

LITAF p.Ala9= (c.27G>A) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 1C (ClinVar).

How common is LITAF p.Ala9= (c.27G>A) in the general population?

LITAF p.Ala9= (c.27G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

LITAF p.Ala9=

c.27G>A · rs149518815 · VCV532706

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

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 -5.3	GERP -3.7
Overall
CADD	7.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,892 alleles

Filtering AF 0.00911% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00855%

Overall 0.00942% 152/1,614,020 alleles · ultra-rare exomes 141/1,461,878 · genomes 11/152,142 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,810
Finnishnot grpmax-eligible	0.0125%	8,004
East Asiangrpmax	0.0111%	8,978
European (non-Finnish)	0.0107%	9,365
South Asian	0.00549%	18,216

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala9=
Coding: c.27G>A
MANE Select: NM_001136472
dbSNP: rs149518815
Type: single nucleotide variant
Location: chr16:11556704 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI 0.02 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 70.60
Residue 9: 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.Ala9Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
LITAF p.Ala9Val Conflicting classifications of pathogenicity ★ ⚠ same residue
LITAF p.Ala9Glu Uncertain significance ★ ⚠ 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

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-ala9 (accessed [today's date]).

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