Is SLTM p.Arg774Ter (c.2320C>T) pathogenic?

SLTM p.Arg774Ter (c.2320C>T) is classified Uncertain significance in SLTM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-05). No allele count reported in gnomAD v4.1 (AN 1,613,432).

How common is SLTM p.Arg774Ter (c.2320C>T) in the general population?

SLTM p.Arg774Ter (c.2320C>T) is no allele count reported in gnomAD v4.1 (AN 1,613,432) (gnomAD).

SLTM p.Arg774Ter

c.2320C>T · VCV4925251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,432)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 17 of 21
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.3	GERP 1.5, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,432). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SLTM
Protein: p.Arg774Ter
Coding: c.2320C>T
MANE Select: NM_024755
Type: single nucleotide variant
Location: chr15:58888440 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 52.38
Residue 774: the 'disordered' region

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

Similar variants

MET p.Arg774= Benign/Likely benign ★★ same residue
MET p.Arg774Thr Uncertain significance ★ ⚠ same residue
SLTM p.Arg774Gln Uncertain significance ★ ⚠ same residue
MET p.His1094Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
MET p.Met1131Thr Pathogenic/Likely pathogenic ★★ same type
MET p.Val1092Ile Pathogenic/Likely pathogenic ★★ same type
MET p.Val1220Ile Pathogenic/Likely pathogenic ★★ same type
MET c.1200+2T>C 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/sltm-p-arg774ter (accessed [today's date]).

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