Is IVD p.Ala417Val (c.1250C>T) pathogenic?

IVD p.Ala417Val (c.1250C>T) is classified Uncertain significance in IVD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-30). AlphaMissense: likely benign (0.2655); Very rare (popmax 0.00203%, nfe); Associated with Inborn genetic diseases.

What condition is associated with IVD p.Ala417Val (c.1250C>T)?

IVD p.Ala417Val (c.1250C>T) is associated with Inborn genetic diseases (ClinVar).

How common is IVD p.Ala417Val (c.1250C>T) in the general population?

IVD p.Ala417Val (c.1250C>T) is very rare (popmax 0.00203%, nfe) (gnomAD).

What do computational predictors say about IVD p.Ala417Val (c.1250C>T)?

AlphaMissense predicts likely benign (score 0.2655) — an in-silico prediction, not a clinical call.

IVD p.Ala417Val

c.1250C>T · VCV3531062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2655 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2655	likely benign
REVEL	0.831	moderately pathogenic-leaning
SaProt	LLR -9.13	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 12 kb · p 0.001 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A420V vs ClinVar A417V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,180,024 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00171% 25/1,461,848 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,168
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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: IVD
Protein: p.Ala417Val
Coding: c.1250C>T
MANE Select: NM_002225
Type: single nucleotide variant
Location: chr15:40418241 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.25 · 5 PDB
Residue 417: an α-helix

Full IVD 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

IVD p.Arg50His Pathogenic/Likely pathogenic ★★ same condition
IVD p.Arg18Trp Uncertain significance ★★ ⚠ same condition
IVD p.Arg332His Uncertain significance ★★ ⚠ same condition
IVD p.Arg6Gln Uncertain significance ★★ ⚠ same condition
IVD p.Arg78Pro Uncertain significance ★★ ⚠ same condition
IVD p.Gln136His Uncertain significance ★★ ⚠ same condition
IVD p.Gly127Val Uncertain significance ★★ ⚠ same condition
IVD p.Gly9Trp 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/ivd-p-ala417val (accessed [today's date]).

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