Is CSKMT p.Met116Arg (c.347T>G) pathogenic?

CSKMT p.Met116Arg (c.347T>G) is classified Uncertain significance in CSKMT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: ambiguous (0.5604); Very rare (popmax 0.00127%, nfe).

How common is CSKMT p.Met116Arg (c.347T>G) in the general population?

CSKMT p.Met116Arg (c.347T>G) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about CSKMT p.Met116Arg (c.347T>G)?

AlphaMissense predicts ambiguous (score 0.5604) — an in-silico prediction, not a clinical call.

CSKMT p.Met116Arg

c.347T>G · rs756496301 · VCV3078048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5604	ambiguous
REVEL	0.471	indeterminate
SaProt	LLR -9.45	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 1,168 bp · p 0.082 · regional, not allelic
Overall
CADD	24.4	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 0.00127% European (non-Finnish) · 15/1,180,024 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000991% 16/1,613,992 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)grpmax	0.00127%	78,668

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CSKMT
Protein: p.Met116Arg
Coding: c.347T>G
MANE Select: NM_001043229
dbSNP: rs756496301
Type: single nucleotide variant
Location: chr11:62666675 (GRCh38)
Gene constraint: LOEUF 1.856 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.80

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

Similar variants

CSKMT p.Met116Val Uncertain significance ★ ⚠ same residue
LBHD1 p.Pro116Ala Uncertain significance ★ ⚠ same residue
CSKMT p.Ala135Thr Uncertain significance ★ ⚠ same type
CSKMT p.Ala168Thr Uncertain significance ★ ⚠ same type
CSKMT p.Ala31Thr Uncertain significance ★ ⚠ same type
CSKMT p.Ala71Thr Uncertain significance ★ ⚠ same type
CSKMT p.Arg171Pro Uncertain significance ★ ⚠ same type
CSKMT p.Arg171Trp 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/cskmt-p-met116arg (accessed [today's date]).

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