Is SPEF2 p.Asp287= (c.861C>T) pathogenic?

SPEF2 p.Asp287= (c.861C>T) is classified Benign in SPEF2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-07-15). Common (popmax 76%, eas) — too common for a highly-penetrant pathogenic allele; Associated with spermatogenic failure 43.

What condition is associated with SPEF2 p.Asp287= (c.861C>T)?

SPEF2 p.Asp287= (c.861C>T) is associated with spermatogenic failure 43 (ClinVar).

SPEF2 p.Asp287=

Q: How common is SPEF2 p.Asp287= (c.861C>T) in the general population?

SPEF2 p.Asp287= (c.861C>T) is common (popmax 76%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.861C>T · rs2270558 · VCV403473

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 76%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

spermatogenic failure 43

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.21	GERP -2.6, phastCons 0.99
Overall
CADD	9.783	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 76% East Asian · 34,083/44,820 alleles

Filtering AF 75.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 75.1%

Overall 56.9% 918,115/1,612,478 alleles · common exomes 827,403/1,460,506 · genomes 90,712/151,972 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	76%	1
Admixed American	70.6%	1
African / African-American	68.5%	1
South Asian	65.9%	2
Remaining individualsnot grpmax-eligible	58.2%	2
Ashkenazi Jewishnot grpmax-eligible	56.6%	2
Middle Eastern	54.8%	2
European (non-Finnish)	54.5%	2
Finnishnot grpmax-eligible	49.2%	2
Amishnot grpmax-eligible	48%	2

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: SPEF2
Protein: p.Asp287=
Coding: c.861C>T
MANE Select: NM_024867
dbSNP: rs2270558
Type: single nucleotide variant
Location: chr5:35654609 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.30

Full SPEF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 43 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPEF2 c.1167+46T>C Benign ★★ same condition
SPEF2 c.2914+19T>G Benign ★★ same condition
SPEF2 c.3331-11T>C Benign ★★ same condition
SPEF2 p.Ala904Val Benign ★★ same condition
SPEF2 p.Ala934Pro Benign ★★ same condition
SPEF2 p.Asn714= Benign ★★ same condition
SPEF2 p.Asn71His Benign ★★ same condition
SPEF2 p.Ile193= Benign ★★ 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/spef2-p-asp287 (accessed [today's date]).

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