Is IVD p.Ala2Val (c.5C>T) pathogenic?

IVD p.Ala2Val (c.5C>T) is classified Uncertain significance in IVD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.2048); Ultra-rare (popmax 0.0223%, eas); Associated with Inborn genetic diseases.

What condition is associated with IVD p.Ala2Val (c.5C>T)?

IVD p.Ala2Val (c.5C>T) is associated with Inborn genetic diseases (ClinVar).

How common is IVD p.Ala2Val (c.5C>T) in the general population?

IVD p.Ala2Val (c.5C>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about IVD p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely benign (score 0.2048) — an in-silico prediction, not a clinical call.

IVD p.Ala2Val

c.5C>T · rs200977412 · VCV3112019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2048 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2048	likely benign
REVEL	0.489	indeterminate
SaProt	LLR -8.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 12 kb · p 0.001 · regional, not allelic
Overall
CADD	23.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A5V vs ClinVar A2V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,836 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00917%

Overall 0.00304% 49/1,611,620 alleles · ultra-rare exomes 43/1,459,370 · genomes 6/152,250 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,484
Remaining individualsnot grpmax-eligible	0.00642%	15,584
African / African-American	0.00401%	24,954
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,544
European (non-Finnish)	0.00263%	38,014

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.Ala2Val
Coding: c.5C>T
MANE Select: NM_002225
dbSNP: rs200977412
Type: single nucleotide variant
Location: chr15:40405832 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.25 · 5 PDB

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.Ala2= Likely benign ★ same residue
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

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-ala2val (accessed [today's date]).

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