Is SEC23A p.Phe94Ser (c.281T>C) pathogenic?

SEC23A p.Phe94Ser (c.281T>C) is classified Uncertain significance in SEC23A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-16). AlphaMissense: likely pathogenic (0.9996); No allele count reported in gnomAD v4.1 (AN 1,600,176); Associated with craniolenticulosutural dysplasia.

What condition is associated with SEC23A p.Phe94Ser (c.281T>C)?

SEC23A p.Phe94Ser (c.281T>C) is associated with craniolenticulosutural dysplasia (ClinVar).

How common is SEC23A p.Phe94Ser (c.281T>C) in the general population?

SEC23A p.Phe94Ser (c.281T>C) is no allele count reported in gnomAD v4.1 (AN 1,600,176) (gnomAD).

What do computational predictors say about SEC23A p.Phe94Ser (c.281T>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

SEC23A p.Phe94Ser

c.281T>C · rs1594483924 · VCV2110245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,176)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

craniolenticulosutural dysplasia

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 2% in SEC23A
REVEL	0.897	moderately pathogenic-leaning
SaProt	LLR -14.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 53 kb · p 0.001 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,600,176). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SEC23A
Protein: p.Phe94Ser
Coding: c.281T>C
MANE Select: NM_006364
dbSNP: rs1594483924
Type: single nucleotide variant
Location: chr14:39092626 (GRCh38)
Gene constraint: LOEUF 0.708 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.86 · 38 PDB

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-phe94ser (accessed [today's date]).

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