Is SEC24D p.Asp605Val (c.1814A>T) pathogenic?

SEC24D p.Asp605Val (c.1814A>T) is classified Uncertain significance in SEC24D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-22). AlphaMissense: likely pathogenic (0.5724); Very rare (popmax 8.66e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SEC24D p.Asp605Val (c.1814A>T)?

SEC24D p.Asp605Val (c.1814A>T) is associated with Inborn genetic diseases (ClinVar).

How common is SEC24D p.Asp605Val (c.1814A>T) in the general population?

SEC24D p.Asp605Val (c.1814A>T) is very rare (popmax 8.66e-05%, nfe) (gnomAD).

What do computational predictors say about SEC24D p.Asp605Val (c.1814A>T)?

AlphaMissense predicts likely pathogenic (score 0.5724) — an in-silico prediction, not a clinical call.

SEC24D p.Asp605Val

c.1814A>T · VCV4837779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5724 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.66e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5724	likely pathogenic
REVEL	0.867	moderately pathogenic-leaning
SaProt	LLR -12.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 110 kb · p 0.00018 · regional, not allelic
Overall
CADD	28.4	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

Grpmax group 8.66e-05% European (non-Finnish) · 1/1,154,596 alleles

Overall 6.98e-05% 1/1,432,728 alleles · very rare

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: SEC24D
Protein: p.Asp605Val
Coding: c.1814A>T
MANE Select: NM_014822
Type: single nucleotide variant
Location: chr4:118744954 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.21 · 6 PDB

Full SEC24D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SEC24D c.1824+1G>T Likely pathogenic ★★ same condition
SEC24D p.Ala218Val Uncertain significance ★★ ⚠ same condition
SEC24D p.Ala570Val Uncertain significance ★★ ⚠ same condition
SEC24D p.Ala774Asp Uncertain significance ★★ ⚠ same condition
SEC24D p.Ala94Thr Uncertain significance ★★ ⚠ same condition
SEC24D p.Arg365Thr Uncertain significance ★★ ⚠ same condition
SEC24D p.Asp1018Asn Uncertain significance ★★ ⚠ same condition
SEC24D p.Asp429Tyr 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/sec24d-p-asp605val (accessed [today's date]).

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