Is C6 p.Arg150His (c.449G>A) pathogenic?

C6 p.Arg150His (c.449G>A) is classified Uncertain significance in C6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-25). AlphaMissense: likely benign (0.1233); Very rare (popmax 0.00668%, afr); Associated with Inborn genetic diseases.

What condition is associated with C6 p.Arg150His (c.449G>A)?

C6 p.Arg150His (c.449G>A) is associated with Inborn genetic diseases (ClinVar).

How common is C6 p.Arg150His (c.449G>A) in the general population?

C6 p.Arg150His (c.449G>A) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about C6 p.Arg150His (c.449G>A)?

AlphaMissense predicts likely benign (score 0.1233) — an in-silico prediction, not a clinical call.

C6 p.Arg150His

c.449G>A · rs371223066 · VCV1463793

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1233 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1233	likely benign
REVEL	0.761	pathogenic-leaning
SaProt	LLR -10.41	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.94, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 60 kb · p 0.0034 · regional, not allelic
Overall
CADD	26.1	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 0.00668% African / African-American · 5/74,888 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00161% 26/1,613,534 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,978
European (non-Finnish)	0.00161%	62,097
Finnishnot grpmax-eligible	0.00157%	63,864
South Asian	0.0011%	91,082

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: C6
Protein: p.Arg150His
Coding: c.449G>A
MANE Select: NM_000065
dbSNP: rs371223066
Type: single nucleotide variant
Location: chr5:41195930 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.72 · 11 PDB
Residue 150: a disulfide bond; the ldl-receptor class a domain

Full C6 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

C6 p.Arg150Leu Uncertain significance ★ ⚠ same residue
C6 p.Arg150Cys Uncertain significance ★ ⚠ same residue
C6 p.Ala396Gly Uncertain significance ★★ ⚠ same condition
C6 p.Ala456Thr Uncertain significance ★★ ⚠ same condition
C6 p.Ala500Ser Uncertain significance ★★ ⚠ same condition
C6 p.Arg108His Uncertain significance ★★ ⚠ same condition
C6 p.Arg145His Uncertain significance ★★ ⚠ same condition
C6 p.Arg182Gln 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/c6-p-arg150his (accessed [today's date]).

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