Is C2 p.Val113Met (c.337G>A) pathogenic?

C2 p.Val113Met (c.337G>A) is classified Uncertain significance in C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-16). AlphaMissense: likely benign (0.1634); Absent from gnomAD v4.1; Associated with complement component 2 deficiency.

What condition is associated with C2 p.Val113Met (c.337G>A)?

C2 p.Val113Met (c.337G>A) is associated with complement component 2 deficiency, age related macular degeneration 14 (ClinVar).

How common is C2 p.Val113Met (c.337G>A) in the general population?

C2 p.Val113Met (c.337G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C2 p.Val113Met (c.337G>A)?

AlphaMissense predicts likely benign (score 0.1634) — an in-silico prediction, not a clinical call.

C2 p.Val113Met

Q: How is Immunodeficiency due to a classical component pathway complement deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.337G>A · rs1769482101 · VCV905374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1634 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

complement component 2 deficiency

Computational evidence

Protein change
AlphaMissense	0.1634	likely benign
REVEL	0.369	indeterminate
SaProt	LLR -7.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.045	GERP -3.3, phastCons 0.012
Regional constraint	o/e 0.84	unconstrained · MANE · 18 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	17.36	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: C2
Protein: p.Val113Met
Coding: c.337G>A
MANE Select: NM_000063
dbSNP: rs1769482101
Type: single nucleotide variant
Location: chr6:31928812 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 113: a disulfide bond; the sushi 2 domain; a β-strand

Full C2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complement component 2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: age related macular degeneration 14

For Immunodeficiency due to a classical component pathway complement deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

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C2 p.Asp390Ala Uncertain significance ★★ ⚠ same condition
C2 p.Asp661Asn Uncertain significance ★★ ⚠ same condition
C2 p.Lys572Asn Uncertain significance ★★ ⚠ same condition
C2 p.Phe273= Uncertain significance ★★ same condition
C2 p.Phe95Val 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/c2-p-val113met (accessed [today's date]).

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