Is CHIA p.Ile13Val (c.37A>G) pathogenic?

CHIA p.Ile13Val (c.37A>G) is classified Likely benign in CHIA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely benign (0.0721); Very rare (popmax 8.47e-05%, nfe).

How common is CHIA p.Ile13Val (c.37A>G) in the general population?

CHIA p.Ile13Val (c.37A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CHIA p.Ile13Val (c.37A>G)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

CHIA p.Ile13Val

c.37A>G · VCV4653375

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0721 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0721	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -5.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.21	GERP -1.5, phastCons 0.007
Regional constraint	o/e 1.10	unconstrained · MANE · 9,995 bp · p 0.014 · regional, not allelic
Overall
CADD	7.86	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,946 alleles

Overall 6.84e-05% 1/1,461,796 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: CHIA
Protein: p.Ile13Val
Coding: c.37A>G
MANE Select: NM_201653
Type: single nucleotide variant
Location: chr1:111311700 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.65 · 8 PDB

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

Similar variants

CHIA p.Ala295Thr Benign/Likely benign ★★ same type
CHIA p.Ala57Thr Likely benign ★★ ⚠ same type
CHIA p.Arg35Trp Benign ★★ ⚠ same type
CHIA p.Gly317Glu Benign ★★ same type
CHIA p.Gly356= Benign ★★ same type
CHIA p.Ile272= Benign ★★ same type
CHIA p.Lys251= Benign ★★ same type
CHIA p.Ala182Thr Uncertain significance ★ ⚠ 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/chia-p-ile13val (accessed [today's date]).

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