Is SEC23A p.Ala687= (c.2061C>A) pathogenic?

SEC23A p.Ala687= (c.2061C>A) is classified Likely benign in SEC23A (ClinVar, Single submitter, 2 submitters; last evaluated 2024-05-23). Ultra-rare (popmax 0.0258%, nfe); Associated with craniolenticulosutural dysplasia.

What condition is associated with SEC23A p.Ala687= (c.2061C>A)?

SEC23A p.Ala687= (c.2061C>A) is associated with craniolenticulosutural dysplasia (ClinVar).

How common is SEC23A p.Ala687= (c.2061C>A) in the general population?

SEC23A p.Ala687= (c.2061C>A) is ultra-rare (popmax 0.0258%, nfe) (gnomAD).

SEC23A p.Ala687=

c.2061C>A · rs373104799 · VCV3054234

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0258%, nfe)

Conditions

craniolenticulosutural dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.053	GERP 0.16, phastCons 0.56
Overall
CADD	7.838	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0258% European (non-Finnish) · 304/1,180,032 alleles

Filtering AF 0.0233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0224%

Overall 0.0201% 324/1,613,988 alleles · ultra-rare exomes 309/1,461,880 · genomes 15/152,108 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0258%	3,882
Remaining individualsnot grpmax-eligible	0.0224%	4,463
African / African-American	0.00801%	12,481

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: SEC23A
Protein: p.Ala687=
Coding: c.2061C>A
MANE Select: NM_006364
dbSNP: rs373104799
Type: single nucleotide variant
Location: chr14:39040813 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.86 · 38 PDB
Residue 687: an α-helix

Full SEC23A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

craniolenticulosutural dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SEC23A p.Ala284Pro Uncertain significance ★★ ⚠ same condition
SEC23A p.Ala478Ser Uncertain significance ★★ ⚠ same condition
SEC23A p.Arg123Cys Uncertain significance ★★ ⚠ same condition
SEC23A p.Arg476His Uncertain significance ★★ ⚠ same condition
SEC23A p.Arg67His Uncertain significance ★★ ⚠ same condition
SEC23A p.Arg716Cys Uncertain significance ★★ ⚠ same condition
SEC23A p.Asn680Asp Uncertain significance ★★ ⚠ same condition
SEC23A p.Cys180Tyr 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/sec23a-p-ala687 (accessed [today's date]).

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