Is SUN5 p.Val128fs (c.381del) pathogenic?

SUN5 p.Val128fs (c.381del) is classified Pathogenic/Likely pathogenic in SUN5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-09-01). Rare (popmax 0.138%, eas); Associated with spermatogenic failure 16.

What condition is associated with SUN5 p.Val128fs (c.381del)?

SUN5 p.Val128fs (c.381del) is associated with spermatogenic failure 16 (ClinVar).

How common is SUN5 p.Val128fs (c.381del) in the general population?

SUN5 p.Val128fs (c.381del) is rare (popmax 0.138%, eas) (gnomAD).

SUN5 p.Val128fs

c.381del · rs781693813 · VCV268050

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.138%, eas)

Conditions

spermatogenic failure 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.21	GERP 0.012, phastCons 0.46
Overall
CADD	23.2	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

Grpmax group 0.138% East Asian · 62/44,882 alleles

Filtering AF 0.111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00403% 65/1,613,894 alleles · rare exomes 58/1,461,770 · genomes 7/152,124 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.138%	724
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	8.47e-05%	1,179,967

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: SUN5
Protein: p.Val128fs
Coding: c.381del
MANE Select: NM_080675
dbSNP: rs781693813
Type: Deletion
Location: chr20:32997647 (GRCh38)
Gene constraint: LOEUF 1.146 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.31

Full SUN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SUN5 p.Arg356Cys Likely pathogenic ★★ same condition
SUN5 c.211+1_211+2dupGT Likely pathogenic ★ same condition
SUN5 p.Arg149Ter Likely pathogenic ★ same condition
SUN5 p.Met162Lys Pathogenic ⚠ same condition
SUN5 p.Ser284Ter Pathogenic same condition
SUN5 p.Thr275Met Pathogenic same condition
SUN5 p.Val261Met Pathogenic same condition

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/sun5-p-val128fs (accessed [today's date]).

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