Is CARNMT1 p.Ile248Val (c.742A>G) pathogenic?

CARNMT1 p.Ile248Val (c.742A>G) is classified Uncertain significance in CARNMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.0596); Ultra-rare (popmax 0.0817%, eas).

How common is CARNMT1 p.Ile248Val (c.742A>G) in the general population?

CARNMT1 p.Ile248Val (c.742A>G) is ultra-rare (popmax 0.0817%, eas) (gnomAD).

What do computational predictors say about CARNMT1 p.Ile248Val (c.742A>G)?

AlphaMissense predicts likely benign (score 0.0596) — an in-silico prediction, not a clinical call.

CARNMT1 p.Ile248Val

c.742A>G · rs770202789 · VCV3137391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0596 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0817%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0596	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -3.83	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 1.6	GERP -0.57, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 34 kb · p 3.4e-09 · regional, not allelic
Overall
CADD	14.81	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 0.0817% East Asian · 35/42,816 alleles

Filtering AF 0.0604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.053%

Overall 0.00238% 36/1,515,104 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0817%	1,223
Remaining individualsnot grpmax-eligible	0.00174%	57,406

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.Ile248Val
Coding: c.742A>G
MANE Select: NM_152420
dbSNP: rs770202789
Type: single nucleotide variant
Location: chr9:74998766 (GRCh38)
Gene constraint: LOEUF 1.157 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.52 · 3 PDB

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.Arg63His 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

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-ile248val (accessed [today's date]).

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