Is C2 p.Val618= (c.1854C>T) pathogenic?

C2 p.Val618= (c.1854C>T) is classified Likely benign in C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Very rare (popmax 0.00833%, amr).

How common is C2 p.Val618= (c.1854C>T) in the general population?

C2 p.Val618= (c.1854C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

C2 p.Val618=

c.1854C>T · rs772507515 · VCV2081766

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Pangolin	Δ0.20	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 0.88	GERP -3.1, phastCons 1
Overall
CADD	13.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/59,992 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00089% 13/1,460,528 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	11,998
African / African-American	0.00134%	74,888
South Asian	0.0011%	91,076
European (non-Finnish)	0.000509%	196,634

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: C2
Protein: p.Val618=
Coding: c.1854C>T
MANE Select: NM_000063
dbSNP: rs772507515
Type: single nucleotide variant
Location: chr6:31944178 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 618: a β-strand; the peptidase s1 domain

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

Similar variants

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C2 c.2029+5G>A Uncertain significance ★★ same type
C2 p.Ala363Thr Uncertain significance ★★ ⚠ same type
C2 p.Ala682Glu Uncertain significance ★★ ⚠ same type
C2 p.Arg124Gln Uncertain significance ★★ ⚠ same type
C2 p.Arg129His Uncertain significance ★★ same type
C2 p.Arg174Cys Uncertain significance ★★ ⚠ same type
C2 p.Arg176Cys 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/c2-p-val618 (accessed [today's date]).

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