Is C4A p.Val897Ile (c.2689G>A) pathogenic?

C4A p.Val897Ile (c.2689G>A) is classified Uncertain significance in C4A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). AlphaMissense: likely benign (0.08); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with C4A p.Val897Ile (c.2689G>A)?

C4A p.Val897Ile (c.2689G>A) is associated with Inborn genetic diseases (ClinVar).

How common is C4A p.Val897Ile (c.2689G>A) in the general population?

C4A p.Val897Ile (c.2689G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about C4A p.Val897Ile (c.2689G>A)?

AlphaMissense predicts likely benign (score 0.08) — an in-silico prediction, not a clinical call.

C4A p.Val897Ile

c.2689G>A · VCV3262511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.08 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.08	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 1.7, phastCons 0.99
Overall
CADD	19.7	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 0.00223% East Asian · 1/44,886 alleles

Overall 0.000139% 2/1,441,688 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
South Asian	0.0011%	91,064

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: C4A
Protein: p.Val897Ile
Coding: c.2689G>A
MANE Select: NM_007293
Type: single nucleotide variant
Location: chr6:31994594 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 83.56 · 12 PDB

Full C4A 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

C4B p.Val897Leu Uncertain significance ★ ⚠ same residue
C4A p.Ala1062Val Uncertain significance ★ ⚠ same condition
C4A p.Ala1080Gly Uncertain significance ★ ⚠ same condition
C4A p.Ala1148Val Uncertain significance ★ ⚠ same condition
C4A p.Ala1190Ser Uncertain significance ★ ⚠ same condition
C4A p.Ala1199Thr Uncertain significance ★ ⚠ same condition
C4A p.Ala1205Val Uncertain significance ★ ⚠ same condition
C4A p.Ala1259Thr 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/c4a-p-val897ile (accessed [today's date]).

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