Is GHSR p.Ser349fs (c.1044del) pathogenic?

GHSR p.Ser349fs (c.1044del) is classified Uncertain significance in GHSR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-19). Absent from gnomAD.

How common is GHSR p.Ser349fs (c.1044del) in the general population?

GHSR p.Ser349fs (c.1044del) is absent from gnomAD (gnomAD).

GHSR p.Ser349fs

c.1044del · rs2473554170 · VCV2025005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: GHSR
Protein: p.Ser349fs
Coding: c.1044del
MANE Select: NM_198407
dbSNP: rs2473554170
Type: Deletion
Location: chr3:172445218 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 10 PDB

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

Similar variants

GHSR p.Met264fs Uncertain significance ★★ same type
GHSR p.Phe12fs Uncertain significance ★★ same type
GHSR p.Phe279fs Uncertain significance ★★ same type
GHSR p.Thr64fs Uncertain significance ★★ same type
GHSR c.796+1039_830del Uncertain significance ★ same type
GHSR p.Gly293fs Uncertain significance ★ same type
GHSR p.Ser233fs Uncertain significance ★ same type
GHSR p.Gln36del Likely benign ★ 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/ghsr-p-ser349fs (accessed [today's date]).

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