Is SEMA4A p.Pro562= (c.1686G>T) pathogenic?

SEMA4A p.Pro562= (c.1686G>T) is classified Likely benign in SEMA4A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). Very rare (popmax 8.51e-05%, nfe).

How common is SEMA4A p.Pro562= (c.1686G>T) in the general population?

SEMA4A p.Pro562= (c.1686G>T) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

SEMA4A p.Pro562=

c.1686G>T · rs770648240 · VCV1647085

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

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 -1.6	GERP -3.8
Overall
CADD	0.674	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,174,668 alleles

Overall 6.24e-05% 1/1,603,844 alleles · very rare exomes 1/1,451,516 · genomes 0/152,328 · 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: SEMA4A
Protein: p.Pro562=
Coding: c.1686G>T
MANE Select: NM_022367
dbSNP: rs770648240
Type: single nucleotide variant
Location: chr1:156175649 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.05

Full SEMA4A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEMA4A p.Pro562Leu Uncertain significance ★★ ⚠ same residue
SEMA4A c.*208A>G Uncertain significance ★★ same type
SEMA4A p.Ala114Thr Uncertain significance ★★ ⚠ same type
SEMA4A p.Ala181Thr Uncertain significance ★★ ⚠ same type
SEMA4A p.Ala337Val Uncertain significance ★★ same type
SEMA4A p.Ala446Val Uncertain significance ★★ ⚠ same type
SEMA4A p.Ala509Gly Uncertain significance ★★ ⚠ same type
SEMA4A p.Ala570Thr 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/sema4a-p-pro562 (accessed [today's date]).

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