Is SUN5 p.Arg149Ter (c.445C>T) pathogenic?

SUN5 p.Arg149Ter (c.445C>T) is classified Likely pathogenic in SUN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-04). Very rare (popmax 0.00475%, nfe); Associated with spermatogenic failure 16.

What condition is associated with SUN5 p.Arg149Ter (c.445C>T)?

SUN5 p.Arg149Ter (c.445C>T) is associated with spermatogenic failure 16 (ClinVar).

How common is SUN5 p.Arg149Ter (c.445C>T) in the general population?

SUN5 p.Arg149Ter (c.445C>T) is very rare (popmax 0.00475%, nfe) (gnomAD).

SUN5 p.Arg149Ter

c.445C>T · VCV4077674

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00475%, nfe)

Conditions

spermatogenic failure 16

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
NMD	predicted	premature termination codon in exon 8 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.87, phastCons 0.18
Overall
CADD	37.0	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

Grpmax group 0.00475% European (non-Finnish) · 56/1,179,952 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00384% 62/1,613,984 alleles · very rare exomes 57/1,461,794 · genomes 5/152,190 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00475%	21,071
South Asian	0.00329%	30,354
African / African-American	0.00267%	37,497
Remaining individualsnot grpmax-eligible	0.0016%	62,500

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.Arg149Ter
Coding: c.445C>T
MANE Select: NM_080675
Type: single nucleotide variant
Location: chr20:32995708 (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 p.Met162Lys Pathogenic ⚠ same condition
SUN5 p.Ser284Ter Pathogenic same condition
SUN5 p.Thr275Met Pathogenic same condition
SUN5 p.Val261Met Pathogenic same condition
SUN5 p.Val128fs Pathogenic/Likely pathogenic ★★ same condition
SUN5 c.211+1_211+2dupGT Likely pathogenic ★ same condition
SUN5 c.984+8C>T 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/sun5-p-arg149ter (accessed [today's date]).

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