Is SEMA3E p.Arg693= (c.2079G>A) pathogenic?

SEMA3E p.Arg693= (c.2079G>A) is classified Likely benign in SEMA3E (ClinVar, Single submitter, 2 submitters; last evaluated 2022-08-14). Very rare (popmax 0.00935%, afr); Associated with CHARGE syndrome.

What condition is associated with SEMA3E p.Arg693= (c.2079G>A)?

SEMA3E p.Arg693= (c.2079G>A) is associated with CHARGE syndrome (ClinVar).

How common is SEMA3E p.Arg693= (c.2079G>A) in the general population?

SEMA3E p.Arg693= (c.2079G>A) is very rare (popmax 0.00935%, afr) (gnomAD).

SEMA3E p.Arg693=

c.2079G>A · rs754284987 · VCV2145629

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Conditions

CHARGE syndrome

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 2.2	GERP 0.98, phastCons 1
Overall
CADD	8.943	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,892 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000558% 9/1,613,616 alleles · very rare exomes 3/1,461,490 · genomes 6/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,699
European (non-Finnish)	0.00017%	589,873

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: SEMA3E
Protein: p.Arg693=
Coding: c.2079G>A
MANE Select: NM_012431
dbSNP: rs754284987
Type: single nucleotide variant
Location: chr7:83367835 (GRCh38)
Gene constraint: LOEUF 0.668 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.62

Full SEMA3E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CHARGE syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SEMA3E c.1500+5G>A Uncertain significance ★★ same condition
SEMA3E p.Ala112Val Uncertain significance ★★ ⚠ same condition
SEMA3E p.Ala290Val Uncertain significance ★★ ⚠ same condition
SEMA3E p.Ala383Ser Uncertain significance ★★ ⚠ same condition
SEMA3E p.Ala414Thr Uncertain significance ★★ ⚠ same condition
SEMA3E p.Ala437Thr Uncertain significance ★★ ⚠ same condition
SEMA3E p.Ala508Thr Uncertain significance ★★ ⚠ same condition
SEMA3E p.Ala609Val Uncertain significance ★★ ⚠ 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/sema3e-p-arg693 (accessed [today's date]).

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