Is C1R p.Met112Val (c.334A>G) pathogenic?

C1R p.Met112Val (c.334A>G) is classified Conflicting classifications of pathogenicity in C1R (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.3216); Rare (popmax 0.157%, afr); Associated with C1R-related disorder.

What condition is associated with C1R p.Met112Val (c.334A>G)?

C1R p.Met112Val (c.334A>G) is associated with C1R-related disorder (ClinVar).

How common is C1R p.Met112Val (c.334A>G) in the general population?

C1R p.Met112Val (c.334A>G) is rare (popmax 0.157%, afr) (gnomAD).

What do computational predictors say about C1R p.Met112Val (c.334A>G)?

AlphaMissense predicts likely benign (score 0.3216) — an in-silico prediction, not a clinical call.

C1R p.Met112Val

c.334A>G · rs149665060 · VCV2634200

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3216 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.157%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

C1R-related disorder

Computational evidence

Protein change
AlphaMissense	0.3216	likely benign
REVEL	0.423	indeterminate
SaProt	LLR -9.03	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 3.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 10 kb · p 1.4e-08 · regional, not allelic
Overall
CADD	24.2	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 0.157% African / African-American · 93/59,166 alleles

Filtering AF 0.131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.122%

Overall 0.0148% 115/774,936 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.157%	636
Middle Eastern	0.0451%	2,218
Remaining individualsnot grpmax-eligible	0.0257%	3,890
Admixed American	0.0172%	5,818
South Asian	0.00137%	73,216

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: C1R
Protein: p.Met112Val
Coding: c.334A>G
MANE Select: NM_001733
dbSNP: rs149665060
Type: single nucleotide variant
Location: chr12:7090146 (GRCh38)
Gene constraint: LOEUF 0.635 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 87.33 · 12 PDB
Residue 112: the cub 1 domain

Full C1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

C1R-related disorder

Similar variants

C1R p.Met112Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
C1R p.Cys309Gly Likely pathogenic ★ same condition
C1R p.Cys338Tyr Likely pathogenic ★ same condition
C1R p.Asp294Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
C1R c.3-93G>A Benign same condition
C1R c.916+10C>T Likely benign same condition
C1R p.Thr671= Likely benign same condition
C1R p.Arg301Pro Pathogenic ★★ ⚠ 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/c1r-p-met112val (accessed [today's date]).

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