Is CANX p.Asp34His (c.100G>C) pathogenic?

CANX p.Asp34His (c.100G>C) is classified Uncertain significance in CANX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: ambiguous (0.3918); Very rare (popmax 0.00195%, nfe).

How common is CANX p.Asp34His (c.100G>C) in the general population?

CANX p.Asp34His (c.100G>C) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about CANX p.Asp34His (c.100G>C)?

AlphaMissense predicts ambiguous (score 0.3918) — an in-silico prediction, not a clinical call.

CANX p.Asp34His

c.100G>C · rs1366842266 · VCV2308584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3918 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3918	ambiguous
REVEL	0.207	benign-leaning
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.79, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 15 kb · p 7e-05 · regional, not allelic
Overall
CADD	28.9	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 0.00195% European (non-Finnish) · 23/1,177,810 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00158% 23/1,459,390 alleles · very rare

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.Asp34His
Coding: c.100G>C
MANE Select: NM_001746
dbSNP: rs1366842266
Type: single nucleotide variant
Location: chr5:179705781 (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-asp34his (accessed [today's date]).

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