Is ANTKMT p.Arg63Pro (c.188G>C) pathogenic?

ANTKMT p.Arg63Pro (c.188G>C) is classified Uncertain significance in ANTKMT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.2607); Very rare (popmax 0.00196%, amr).

How common is ANTKMT p.Arg63Pro (c.188G>C) in the general population?

ANTKMT p.Arg63Pro (c.188G>C) is very rare (popmax 0.00196%, amr) (gnomAD).

What do computational predictors say about ANTKMT p.Arg63Pro (c.188G>C)?

AlphaMissense predicts likely benign (score 0.2607) — an in-silico prediction, not a clinical call.

ANTKMT p.Arg63Pro

c.188G>C · rs911067074 · VCV3127218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2607	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -9.38	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 1.2	GERP -3.1, phastCons 0.22
Regional constraint	o/e 1.28	unconstrained · MANE · 1,279 bp · p 3.5e-07 · regional, not allelic
Overall
CADD	22.2	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 0.00196% Admixed American · 1/51,022 alleles

Filtering AF 0.000441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000322%

Overall 0.00079% 11/1,393,194 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00196%	51,022
European (non-Finnish)	0.000873%	114,600

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: ANTKMT
Protein: p.Arg63Pro
Coding: c.188G>C
MANE Select: NM_023933
dbSNP: rs911067074
Type: single nucleotide variant
Location: chr16:721623 (GRCh38)
Gene constraint: LOEUF 1.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.01
Residue 63: the 'methyltransferase (mtase)' region; the 'pre-methyltransferase (premt)' region

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

Similar variants

ANTKMT p.Ala169Thr Uncertain significance ★ ⚠ same type
ANTKMT p.Ala196Ser Uncertain significance ★ ⚠ same type
ANTKMT p.Ala209Ser Uncertain significance ★ ⚠ same type
ANTKMT p.Ala224Asp Uncertain significance ★ ⚠ same type
ANTKMT p.Ala224Ser Uncertain significance ★ ⚠ same type
ANTKMT p.Ala36Thr Uncertain significance ★ ⚠ same type
ANTKMT p.Ala62Ser Uncertain significance ★ ⚠ same type
ANTKMT p.Ala92Val 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/antkmt-p-arg63pro (accessed [today's date]).

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