Is SEC23A p.Pro701= (c.2103A>G) pathogenic?

SEC23A p.Pro701= (c.2103A>G) is classified Likely benign in SEC23A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-29). Very rare (popmax 0.004%, afr); Associated with craniolenticulosutural dysplasia.

What condition is associated with SEC23A p.Pro701= (c.2103A>G)?

SEC23A p.Pro701= (c.2103A>G) is associated with craniolenticulosutural dysplasia (ClinVar).

How common is SEC23A p.Pro701= (c.2103A>G) in the general population?

SEC23A p.Pro701= (c.2103A>G) is very rare (popmax 0.004%, afr) (gnomAD).

SEC23A p.Pro701=

c.2103A>G · VCV4749885

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

craniolenticulosutural dysplasia

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 -1.3	GERP -3.8, phastCons 0.001
Overall
CADD	5.752	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,938 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,614,102 alleles · very rare exomes 1/1,461,872 · genomes 3/152,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,979
European (non-Finnish)	8.47e-05%	1,180,048

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.Pro701=
Coding: c.2103A>G
MANE Select: NM_006364
Type: single nucleotide variant
Location: chr14:39040771 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.86 · 38 PDB
Residue 701: a β-strand

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-pro701 (accessed [today's date]).

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