Is CANX p.Ile17Val (c.49A>G) pathogenic?

CANX p.Ile17Val (c.49A>G) is classified Likely benign in CANX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.0561); Very rare (popmax 0.0011%, sas).

How common is CANX p.Ile17Val (c.49A>G) in the general population?

CANX p.Ile17Val (c.49A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CANX p.Ile17Val (c.49A>G)?

AlphaMissense predicts likely benign (score 0.0561) — an in-silico prediction, not a clinical call.

CANX p.Ile17Val

c.49A>G · VCV4218687

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0561 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0561	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.74	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 -1.9	GERP -3.7
Regional constraint	o/e 0.81	unconstrained · MANE · 15 kb · p 7e-05 · regional, not allelic
Overall
CADD	0.039	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 0.0011% South Asian · 1/91,018 alleles

Overall 0.000137% 2/1,459,898 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,018
European (non-Finnish)	8.49e-05%	1,178,238

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: CANX
Protein: p.Ile17Val
Coding: c.49A>G
MANE Select: NM_001746
Type: single nucleotide variant
Location: chr5:179705730 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.15

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

Similar variants

CANX p.Ala20Ser Uncertain significance ★ ⚠ same type
CANX p.Ala336Thr Uncertain significance ★ ⚠ same type
CANX p.Ala421Val Uncertain significance ★ ⚠ same type
CANX p.Ala460Thr Uncertain significance ★ ⚠ same type
CANX p.Arg415Ile Uncertain significance ★ ⚠ same type
CANX p.Arg480Leu Uncertain significance ★ ⚠ same type
CANX p.Arg590Gln Uncertain significance ★ ⚠ same type
CANX p.Asp142Gly 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/canx-p-ile17val (accessed [today's date]).

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