Is SEC24C p.Ser72Ala (c.214T>G) pathogenic?

SEC24C p.Ser72Ala (c.214T>G) is classified Uncertain significance in SEC24C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0615); Absent from gnomAD v4.1.

How common is SEC24C p.Ser72Ala (c.214T>G) in the general population?

SEC24C p.Ser72Ala (c.214T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SEC24C p.Ser72Ala (c.214T>G)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

SEC24C p.Ser72Ala

c.214T>G · VCV4161776

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 14 kb · p 0.5 · regional, not allelic
Overall
CADD	18.53	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SEC24C
Protein: p.Ser72Ala
Coding: c.214T>G
MANE Select: NM_198597
Type: single nucleotide variant
Location: chr10:73751149 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.29 · 3 PDB
Residue 72: the 'disordered' region

Full SEC24C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEC24C c.1800-7T>C Benign ★★ same type
SEC24C c.3145-4G>A Benign ★★ same type
SEC24C c.850+10T>G Benign ★★ same type
SEC24C p.Ala566= Benign ★★ same type
SEC24C p.Gly257= Benign/Likely benign ★★ same type
SEC24C p.Pro255Ala Benign ★★ same type
SEC24C p.Pro958= Likely benign ★★ same type
SEC24C p.Thr870= Likely benign ★★ 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/sec24c-p-ser72ala (accessed [today's date]).

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