Is CTTN p.Val164Leu (c.490G>C) pathogenic?

CTTN p.Val164Leu (c.490G>C) is classified Uncertain significance in CTTN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: ambiguous (0.3768); Very rare (popmax 0.00167%, amr).

How common is CTTN p.Val164Leu (c.490G>C) in the general population?

CTTN p.Val164Leu (c.490G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CTTN p.Val164Leu (c.490G>C)?

AlphaMissense predicts ambiguous (score 0.3768) — an in-silico prediction, not a clinical call.

CTTN p.Val164Leu

c.490G>C · VCV3498503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3768 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
AlphaMissense	0.3768	ambiguous
REVEL	0.384	indeterminate
SaProt	LLR -9.87	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP -2.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 14 kb · p 0.00056 · regional, not allelic
Overall
CADD	24.5	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 0.00167% Admixed American · 1/60,004 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,614,066 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
South Asian	0.0011%	91,088
European (non-Finnish)	0.000169%	590,023

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: CTTN
Protein: p.Val164Leu
Coding: c.490G>C
MANE Select: NM_005231
Type: single nucleotide variant
Location: chr11:70417045 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 63.11 · 5 PDB

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

Similar variants

CTTN p.Val164Met Uncertain significance ★ ⚠ same residue
CTTN p.Val312= Benign ★★ same type
CTTN p.Val340Gly Likely benign ★★ same type
CTTN c.*1144C>G Uncertain significance ★ same type
CTTN c.*1145C>T Uncertain significance ★ same type
CTTN c.*1154G>A Uncertain significance ★ same type
CTTN c.*1164C>T Uncertain significance ★ same type
CTTN c.*1167C>T 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/cttn-p-val164leu (accessed [today's date]).

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