Is CLTA p.Ile97Val (c.289A>G) pathogenic?

CLTA p.Ile97Val (c.289A>G) is classified Uncertain significance in CLTA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-04). AlphaMissense: likely benign (0.1355); Very rare (popmax 0.00267%, afr).

How common is CLTA p.Ile97Val (c.289A>G) in the general population?

CLTA p.Ile97Val (c.289A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CLTA p.Ile97Val (c.289A>G)?

AlphaMissense predicts likely benign (score 0.1355) — an in-silico prediction, not a clinical call.

CLTA p.Ile97Val

c.289A>G · rs770633121 · VCV2543488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1355 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1355	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -6.34	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 6.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 21 kb · p 0.34 · regional, not allelic
Overall
CADD	19.3	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 0.00267% African / African-American · 2/74,892 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00211% 34/1,613,716 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,446
European (non-Finnish)	0.00246%	40,681
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,474
South Asian	0.0011%	91,086

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: CLTA
Protein: p.Ile97Val
Coding: c.289A>G
MANE Select: NM_001833
dbSNP: rs770633121
Type: single nucleotide variant
Location: chr9:36199012 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.20 · 1 PDB

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

Similar variants

CLTA c.256-6G>A Benign ★★ same type
CLTA c.486-2284G>A Uncertain significance ★ ⚠ same type
CLTA c.486-971A>G Uncertain significance ★ ⚠ same type
CLTA p.Ala11Gly Uncertain significance ★ ⚠ same type
CLTA p.Ala133Thr Uncertain significance ★ ⚠ same type
CLTA p.Ala18Thr Uncertain significance ★ ⚠ same type
CLTA p.Ala214Pro Uncertain significance ★ ⚠ same type
CLTA p.Ala51Thr Uncertain significance ★ ⚠ same type

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/clta-p-ile97val (accessed [today's date]).

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