Is ANTKMT p.Ser146Pro (c.436T>C) pathogenic?

ANTKMT p.Ser146Pro (c.436T>C) is classified Uncertain significance in ANTKMT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely pathogenic (0.9287); Very rare (popmax 0.00134%, afr).

How common is ANTKMT p.Ser146Pro (c.436T>C) in the general population?

ANTKMT p.Ser146Pro (c.436T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ANTKMT p.Ser146Pro (c.436T>C)?

AlphaMissense predicts likely pathogenic (score 0.9287) — an in-silico prediction, not a clinical call.

ANTKMT p.Ser146Pro

c.436T>C · VCV4111950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9287 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9287	likely pathogenic · top 6% in ANTKMT
REVEL	0.262	benign-leaning
SaProt	LLR -12.53	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 1.28	unconstrained · MANE · 1,279 bp · p 3.5e-07 · regional, not allelic
Overall
CADD	27.0	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 0.00134% African / African-American · 1/74,812 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000684% 11/1,609,064 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,812
European (non-Finnish)	0.000848%	117,898

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.Ser146Pro
Coding: c.436T>C
MANE Select: NM_023933
Type: single nucleotide variant
Location: chr16:722111 (GRCh38)
Gene constraint: LOEUF 1.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.01

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-ser146pro (accessed [today's date]).

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