Is CARNMT1 p.Arg63His (c.188G>A) pathogenic?

CARNMT1 p.Arg63His (c.188G>A) is classified Uncertain significance in CARNMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). AlphaMissense: ambiguous (0.4226); Ultra-rare (popmax 0.0194%, amr).

How common is CARNMT1 p.Arg63His (c.188G>A) in the general population?

CARNMT1 p.Arg63His (c.188G>A) is ultra-rare (popmax 0.0194%, amr) (gnomAD).

What do computational predictors say about CARNMT1 p.Arg63His (c.188G>A)?

AlphaMissense predicts ambiguous (score 0.4226) — an in-silico prediction, not a clinical call.

CARNMT1 p.Arg63His

c.188G>A · rs200933121 · VCV3137388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4226 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4226	ambiguous
REVEL	0.099	moderately benign-leaning
SaProt	LLR -10.65	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 7.3	GERP -0.4, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 11 kb · p 0.16 · regional, not allelic
Overall
CADD	27.2	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 0.0194% Admixed American · 11/56,814 alleles

Filtering AF 0.0109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00835%

Overall 0.00203% 32/1,579,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0194%	5,165
East Asian	0.00492%	20,336
Remaining individualsnot grpmax-eligible	0.00492%	20,345
African / African-American	0.0014%	71,460
European (non-Finnish)	0.00129%	77,674

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: CARNMT1
Protein: p.Arg63His
Coding: c.188G>A
MANE Select: NM_152420
dbSNP: rs200933121
Type: single nucleotide variant
Location: chr9:75028054 (GRCh38)
Gene constraint: LOEUF 1.157 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.52 · 3 PDB
Residue 63: an α-helix

Full CARNMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CARNMT1 p.Asp295= Benign ★★ same type
CARNMT1 p.Ala49Val Uncertain significance ★ ⚠ same type
CARNMT1 p.Arg13Pro Uncertain significance ★ ⚠ same type
CARNMT1 p.Arg83Gln Uncertain significance ★ ⚠ same type
CARNMT1 p.Asn249His Uncertain significance ★ ⚠ same type
CARNMT1 p.Asn288Asp Uncertain significance ★ ⚠ same type
CARNMT1 p.Asn353Ser Uncertain significance ★ ⚠ same type
CARNMT1 p.Asp117Glu 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/carnmt1-p-arg63his (accessed [today's date]).

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