Is GHSR p.Phe279fs (c.834del) pathogenic?

GHSR p.Phe279fs (c.834del) is classified Uncertain significance in GHSR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-22). Very rare (popmax 0.005%, amr).

How common is GHSR p.Phe279fs (c.834del) in the general population?

GHSR p.Phe279fs (c.834del) is very rare (popmax 0.005%, amr) (gnomAD).

GHSR p.Phe279fs

c.834del · rs1249971956 · VCV1448801

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,010 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,613,656 alleles · very rare exomes 3/1,461,320 · genomes 0/152,336 · joint denominator

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: GHSR
Protein: p.Phe279fs
Coding: c.834del
MANE Select: NM_198407
dbSNP: rs1249971956
Type: Deletion
Location: chr3:172445428 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 10 PDB
Residue 279: an α-helix

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.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.Ser349fs 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-phe279fs (accessed [today's date]).

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